The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally,from B.1.17(Alpha), B.1.351(Beta), P.1(Gamma), B.1.617.2(Delta) to B.1.1.529(Omicron). The emerging or r...The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally,from B.1.17(Alpha), B.1.351(Beta), P.1(Gamma), B.1.617.2(Delta) to B.1.1.529(Omicron). The emerging or reemerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics,pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 cells. We utilized both animal models of human ACE2(hACE2)transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.展开更多
Fixed-station sampling design was widely used in fishery-independent surveys because of its characteristics of convenient sampling station setting,but the non-probabilistic(fixed)nature made it more uncertainty of dra...Fixed-station sampling design was widely used in fishery-independent surveys because of its characteristics of convenient sampling station setting,but the non-probabilistic(fixed)nature made it more uncertainty of drawing inferences on population.The performance of fixed-station sampling design for multispecies survey has not been evaluated,and we are uncertain if the design could detect the temporal trends of different populations in multispecies fishery-independent survey.In this study,spatial distribution of abundance indices for three species with different spatial distribution patterns including small yellow croaker(Larimichthys polyactis),whitespotted conger(Conger myriaster)and Fang’s blenny(Enedrias fangi)were simulated using ordinary kriging interpolation as the“true”population distribution.The performance of fixed-station sampling design was compared with simple random sampling design by resampling the simulated“true”populations in this simulation study.The results showed that the fixed-station sampling design had the power to detect the seasonal trends of species abundance.The effectiveness of fixed-station sampling design were different in different species distribution patterns.When the species had even distribution,fixed-station sampling design could get high quality abundance data;when the distribution was uneven with heterogeneity or patchiness,fixed-station sampling design tended to underestimate or overestimate the abundance.Evidently,the estimates of abundance index based on the fixedstation sampling design must be calibrated cautiously while applying them for fisheries stock assessment and management.This study suggested that fixed-station sampling design could catch the temporal dynamics of population abundance,but the abundance estimates from the fixed-station sampling design could not be treated as the absolute estimates of populations.展开更多
Hybrid joints have better tensile properties than pure bonded and bolted bolts,and are increasingly used in the aerospace field.Tensile tests are carried out for the Hybrid Bonded/Bolted(HBB)joints of Carbon Fiber Rei...Hybrid joints have better tensile properties than pure bonded and bolted bolts,and are increasingly used in the aerospace field.Tensile tests are carried out for the Hybrid Bonded/Bolted(HBB)joints of Carbon Fiber Reinforced Polymer(CFRP)laminate and titanium alloy plate under different bolt numbers,and the corresponding load–displacement curves are obtained.At the same time,based on Continuum Damage Mechanics(CDM)theory,which is derived from 3D Hashin failure criteria,and a Cohesive Zone Model(CZM),the tensile strength prediction model of the composite laminate-titanium alloy plate multi-bolted HBB joint was established,and the numerical simulation results were in good agreement with the experimental height,which validate the feasibility of the model.The difference in the bearing capacity of HBB joints under different numbers of bolts is compared and analyzed.On this basis,the influence of inter-bolt distance on the tensile properties of the HBB joints is explored.The results show that the double-nail HBB joints can effectively improve the end warpage and low bearing capacity of the single-nail HBB joints.The tensile failure load of the double-nail HBB joints under the standard lap width(30 mm)is 82.6%higher than that of the single nail,the tensile failure load of the three-bolt HBB joints is 34.1%higher than that of the double nail.For the three-bolt HBB joint,the joint strength is controlled by the adhesive and the external bolt,while the internal bolt is redundant,the hybrid joint can be simplified by reducing the middle bolt.The inter-bolt distance has a great influence on the failure load of the hybrid joint.Increasing the inter-bolt distance can effectively improve the bearing capacity of the structure.展开更多
In response to the current coronavirus disease 2019(COVID-19)pandemic,it is crucial to understand the origin,transmission,and evolution of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which relies on c...In response to the current coronavirus disease 2019(COVID-19)pandemic,it is crucial to understand the origin,transmission,and evolution of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which relies on close surveillance of genomic diversity in clinical samples.Although the mutation at the population level had been extensively investigated,how the mutations evolve at the individual level is largely unknown.Eighteen time-series fecal samples were collected from nine patients with COVID-19 during the convalescent phase.The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method.First,we demonstrated the outstanding performance of the hybrid capture method in detecting intra-host variants.We identified 229 intra-host variants at 182 sites in 18 fecal samples.Among them,nineteen variants presented frequency changes>0.3 within 1-5 days,reflecting highly dynamic intrahost viral populations.Moreover,the evolution of the viral genome demonstrated that the virus was probably viable in the gastrointestinal tract during the convalescent period.Meanwhile,we also found that the same mutation showed a distinct pattern of frequency changes in different individuals,indicating a strong random drift.In summary,dramatic changes of the SARS-CoV-2 genome were detected in fecal samples during the convalescent period;whether the viral load in feces is sufficient to establish an infection warranted further investigation.展开更多
A novel RNA virus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is responsible for the ongoing outbreak of coronavirus disease 2019(COVID-19).Population genetic analysis could be useful for investiga...A novel RNA virus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is responsible for the ongoing outbreak of coronavirus disease 2019(COVID-19).Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19.However,due to extensive sampling bias and existence of infection clusters during the epidemic spread,direct applications of existing approaches can lead to biased parameter estimations and data misinterpretation.In this study,we first present robust estimator for the time to the most recent common ancestor(TMRCA)and the mutation rate,and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2.The mutation rate is inferred to be 8.69×10^(−4) per site per year with a 95%confidence interval(CI)of[8.61×10^(−4),8.77×10^(−4)],and the TMRCA of the samples inferred to be Nov 28,2019 with a 95%CI of[Oct 20,2019,Dec 9,2019].The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market.We further demonstrate that genetic polymorphism patterns,including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters,are similar to those caused by evolutionary forces such as natural selection.Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism of SARS-CoV-2.Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081.展开更多
In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive.By the blind watchmaker arg...In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive.By the blind watchmaker argument,such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.展开更多
We demonstrate an all-fiber Q-switched cylindrical vector laser based on a black phosphorus saturable absorber and a transverse mode converter. The saturable absorber is prepared by incorporating the polyvinyl alcohol...We demonstrate an all-fiber Q-switched cylindrical vector laser based on a black phosphorus saturable absorber and a transverse mode converter. The saturable absorber is prepared by incorporating the polyvinyl alcohol with anti-oxidized black phosphorus nanosheets exfoliated in aqueous poly(dimethyldiallyl ammonium chloride)solution. The mode converter is composed of a tapered two-mode fiber and a single-mode fiber, and it can excite switchable azimuthally and radially polarized beams by modulating the input polarization. By enhancing the pump power from 64.68 to 174.82 mW, the repetition rate of the Q-switched azimuthally/radially polarized laser enlarges from 16.72/19.25 to 30.71/37.82 kHz.展开更多
The surveillance and prevention of pathogenic microbiological contamination are the most important tasks of biosafety management in the lab.There is an urgent need to establish an effective and unbiased method to eval...The surveillance and prevention of pathogenic microbiological contamination are the most important tasks of biosafety management in the lab.There is an urgent need to establish an effective and unbiased method to evaluate and monitor such contamination.This study aims to investigate the utility of next generation sequencing(NGS)method to detect possible contamination in the microbiology laboratory.Environmental samples were taken at multiple sites at the lab including the inner site of centrifuge rotor,the bench used for molecular biological tests,the benches of biosafety cabinets used for viral culture,clinical sample pre-treatment and nucleic acids extraction,by scrubbing the sites using sterile flocked swabs.The extracted total nucleic acids were used to construct the libraries for deep sequencing according to the protocol of Ion Torrent platform.At least 1G raw data was obtained for each sample.The reads of viruses and bacteria accounted for 0.01±0.02%,and 77.76±12.53%of total reads respectively.The viral sequences were likely to be derived from gene amplification products,the nucleic acids contaminated in fetal bovine serum.Reads from environmental microorganisms were also identified.Our results suggested that NGS method was capable of monitoring the nucleic acids contaminations from different sources in the lab,demonstrating its promising utility in monitoring and assessing the risk of potential laboratory contamination.The risk of contamination from reagents,remnant DNA and environment should be considered in data analysis and results interpretation.展开更多
Mid-infrared frequency-comb spectroscopy enables measurement of molecules at megahertz spectral resolution,sub-hertz frequency accuracy,and microsecond acquisition speed.However,the widespread adoption of this techniq...Mid-infrared frequency-comb spectroscopy enables measurement of molecules at megahertz spectral resolution,sub-hertz frequency accuracy,and microsecond acquisition speed.However,the widespread adoption of this technique has been hindered by the complexity and alignment sensitivity of mid-infrared frequency-comb sources.Leveraging the underexplored mid-infrared window of silica fibers presents a promising approach to address these challenges.In this study,we present the first,to the best of our knowledge,experimental demonstration and quantitative numerical description of mid-infrared frequency-comb generation in silica fibers.Our all-silica-fiber frequency comb spans over two octaves(0.8μm to 3.4μm)with a power output of 100 mW in the mid-infrared region.The amplified quantum noise is suppressed using four-cycle(25 fs)driving pulses,with the carrier-envelope offset frequency exhibiting a signal-to-noise ratio of 40 dB and a free-running bandwidth of 90 kHz.Our developed model provides quantitative guidelines for mid-infrared frequency-comb generation in silica fibers,enabling all-fiber frequency-comb spectroscopy in diverse fields such as organic synthesis,pharmacokinetics processes,and environmental monitoring.展开更多
The gut microbiota undergoes substantial changes in COVID-19 patients;yet,the utility of these alterations as prognostic biomarkers at the time of hospital admission,and its correlation with immunological and hematolo...The gut microbiota undergoes substantial changes in COVID-19 patients;yet,the utility of these alterations as prognostic biomarkers at the time of hospital admission,and its correlation with immunological and hematological parameters,remains unclear.The objective of this study is to investigate the gut microbiota's dynamic change in critically ill patients with COVID-19 and evaluate its predictive capability for clinical outcomes alongside immunological and hematological parameters.In this study,anal swabs were consecutively collected from 192 COVID-19 patients(583 samples)upon hospital admission for metagenome sequencing.Simultaneously,blood samples were obtained to measure the concentrations of 27 cytokines and chemokines,along with hematological and biochemical indicators.Our findings indicate a significant correlation between the composition and dynamics of gut microbiota with disease severity and mortality in COVID-19 patients.Recovered patients exhibited a higher abundance of Veillonella and denser interactions among gut commensal bacteria compared to deceased patients.Furthermore,the abundance of gut commensal bacteria exhibited a negative correlation with the concentration of proinflammatory cytokines and organ damage markers.The gut microbiota upon admission showed moderate prognostic prediction ability with an AUC of 0.78,which was less effective compared to predictions based on immunological and hematological parameters(AUC 0.80 and 0.88,respectively).Noteworthy,the integration of these three datasets yielded a higher predictive accuracy(AUC 0.93).Our findings suggest the gut microbiota as an informative biomarker for COVID-19 prognosis,augmenting existing immune and hematological indicators.展开更多
We demonstrate that ferroferric-oxide(Fe_3O_4) nanoparticles exhibit nonlinear saturable absorption property at1.55 μm, and fabricate two filmy saturable absorbers by embedding the nanoparticles into a polyvinyl alco...We demonstrate that ferroferric-oxide(Fe_3O_4) nanoparticles exhibit nonlinear saturable absorption property at1.55 μm, and fabricate two filmy saturable absorbers by embedding the nanoparticles into a polyvinyl alcohol(PVA) film or polyimide(PI) film separately. In the Fe_3O_4-PVA(Fe_3O_4-PI) Q-switched fiber laser, the pulse repetition rate increases from 8.5 kHz(5.5 kHz) to 28 kHz(49 kHz) and the pulse duration decreases from 23.5 μs(47 μs) to 6 μs(3.5 μs) by varying the pump power from 25 m W(23 mW) to 150 m W(650 mW). Experiment results indicate that PI-based saturable absorbers can afford larger powers than PVA-based saturable absorbers, which can be attributed to the higher fusion point of the PI film. The Fe_3O_4-PI saturable absorber exhibits features of high damage threshold, low cost, and good flexibility, which could be applied in fields of near-infrared pulse generation and frequency conversions.展开更多
A new variant of concern for SARS-CoV-2,Omicron(B.1.1.529),was designated by the World Health Organization on November 26,2021.This study analyzed the viral genome sequencing data of 108 samples collected from patient...A new variant of concern for SARS-CoV-2,Omicron(B.1.1.529),was designated by the World Health Organization on November 26,2021.This study analyzed the viral genome sequencing data of 108 samples collected from patients infected with Omicron.First,we found that the enrichment efficiency of viral nucleic acids was reduced due to mutations in the region where the primers anneal to.Second,the Omicron variant possesses an excessive number of mutations compared to other variants circulating at the same time(median:62 vs.45),especially in the Spike gene.Mutations in the Spike gene confer alterations in 32 amino acid residues,more than those observed in other SARS-CoV-2 variants.Moreover,a large number of nonsynonymous mutations occur in the codons for the amino acid residues located on the surface of the Spike protein,which could potentially affect the replication,infectivity,and antigenicity of SARS-CoV-2.Third,there are 53 mutations between the Omicron variant and its closest sequences available in public databases.Many of these mutations were rarely observed in public databases and had a low mutation rate.In addition,the linkage disequilibrium between these mutations was low,with a limited number of mutations concurrently observed in the same genome,suggesting that the Omicron variant would be in a different evolutionary branch from the currently prevalent variants.To improve our ability to detect and track the source of new variants rapidly,it is imperative to further strengthen genomic surveillance and data sharing globally in a timely manner.展开更多
COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Paki...COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF1ab)of this cluster.Furthermore,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introductions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.展开更多
As the globe has witnessed the pandemic,epidemic diseases exert a strong impact on human beings and ecosystems.Since the Sun is the primary energy source of the Earth,some scientific pioneers attempted to search for t...As the globe has witnessed the pandemic,epidemic diseases exert a strong impact on human beings and ecosystems.Since the Sun is the primary energy source of the Earth,some scientific pioneers attempted to search for the discernible relation between solar activity and the incidence of epidemics.In this study,the periodic changes and trends of ancient Chinese epidemic data were analyzed in comparison with those of sunspot numbers,a solar activity proxy.The results show that the epidemic and solar activity changes are in good agreement to a certain extent,especially during the Gleissberg and the de Vries cycles.The wavelet coherence shows that the frequency of the epidemic data and sunspot numbers are highly associated.In addition,results from the ensemble empirical mode decomposition illustrate consistent variations in low-frequency decompositions.This study has important implications for further understanding of the potential impact of solar activity on Earth’s biosphere,the underlying mechanism of which needs further exploration.展开更多
In recent decades,emerging and re-emerging human-infecting pathogens have been represented as huge threats to public health and have become a global concern(1).After outbreaks of two coronaviruses(CoVs),severe acute r...In recent decades,emerging and re-emerging human-infecting pathogens have been represented as huge threats to public health and have become a global concern(1).After outbreaks of two coronaviruses(CoVs),severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)became the first-known pandemic hastening CoV with tremendous wrecking to the world(2).The origin tracing of these emerging pathogens is of great significance in infectious disease prevention and control(3–4).The origin of SARS-CoV-2 remains elusive after the more than 3-year pandemic,though scientists around the world are making great efforts.From the experience of studying many other infectious pathogens,origin tracing is systematic and time-consuming work.The supposed origins of many infectious pathogens are still in debate,including SARS-CoV and human immunodeficiency virus,etc(5).展开更多
We analyzed variations in the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)genome during a flight-related cluster outbreak of coronavirus disease 2019(COVID-19)in Shenzhen,China,to explore the characteri...We analyzed variations in the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)genome during a flight-related cluster outbreak of coronavirus disease 2019(COVID-19)in Shenzhen,China,to explore the characteristics of SARS-CoV-2 transmission and intra-host single nucleotide variations(iSNVs)in a confined space.Thirty-three patients with COVID-19 were sampled,and 14 were resampled 3-31 days later.All 47 nasopharyngeal swabs were deep-sequenced.iSNVs and similarities in the consensus genome sequence were analyzed.Three SARS-CoV-2 variants of concern,Delta(n=31),Beta(n=1),and C.1.2(n=1),were detected among the 33 patients.The viral genome sequences from 30 Delta-positive patients had similar SNVs;14 of these patients provided two successive samples.Overall,the 47 sequenced genomes contained 164 iSNVs.Of the 14 paired(successive)samples,the second samples(T2)contained more iSNVs(median:3;95%confidence interval[95%CI]:2.77-10.22)than did the first samples(T1;median:2;95%CI:1.63-3.74;Wilcoxon test,P=0.021).38 iSNVs were detected in T1 samples,and only seven were also detectable in T2 samples.Notably,T2 samples from two of the 14 paired samples had additional mutations than the T1 samples.The iSNVs of the SARS-CoV-2 genome exhibited rapid dynamic changes during a flight-related cluster outbreak event.Intra-host diversity increased gradually with time,and new site mutations occurred in vivo without a population transmission bottleneck.Therefore,we could not determine the generational relationship from the mutation site changes alone.展开更多
基金supported by the Major Science and Technique Programs in Yunnan Province(grant No.202102AA310055)the Bureau of Frontier Sciences and Education,CAS(grant no.QYZDJ-SSW-SMC005 to Y.G.Y.)+2 种基金the Key project of the CAS“Light of West China”Program(to D.Y.)Yunnan Province(202001AS070023 to D.Y.)Yunnan Fundamental Research Projects(grant No.202201AW070020 to J.Z.)
文摘The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally,from B.1.17(Alpha), B.1.351(Beta), P.1(Gamma), B.1.617.2(Delta) to B.1.1.529(Omicron). The emerging or reemerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics,pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 cells. We utilized both animal models of human ACE2(hACE2)transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.
基金The Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)under contract No.2018SDKJ0501-2the National Key Research and Development Program of China under contract No.2019YFD0901304。
文摘Fixed-station sampling design was widely used in fishery-independent surveys because of its characteristics of convenient sampling station setting,but the non-probabilistic(fixed)nature made it more uncertainty of drawing inferences on population.The performance of fixed-station sampling design for multispecies survey has not been evaluated,and we are uncertain if the design could detect the temporal trends of different populations in multispecies fishery-independent survey.In this study,spatial distribution of abundance indices for three species with different spatial distribution patterns including small yellow croaker(Larimichthys polyactis),whitespotted conger(Conger myriaster)and Fang’s blenny(Enedrias fangi)were simulated using ordinary kriging interpolation as the“true”population distribution.The performance of fixed-station sampling design was compared with simple random sampling design by resampling the simulated“true”populations in this simulation study.The results showed that the fixed-station sampling design had the power to detect the seasonal trends of species abundance.The effectiveness of fixed-station sampling design were different in different species distribution patterns.When the species had even distribution,fixed-station sampling design could get high quality abundance data;when the distribution was uneven with heterogeneity or patchiness,fixed-station sampling design tended to underestimate or overestimate the abundance.Evidently,the estimates of abundance index based on the fixedstation sampling design must be calibrated cautiously while applying them for fisheries stock assessment and management.This study suggested that fixed-station sampling design could catch the temporal dynamics of population abundance,but the abundance estimates from the fixed-station sampling design could not be treated as the absolute estimates of populations.
基金co-supported by the National Natural Science Foundation of China(No.U1833116)Key Scientific Research Project of Colleges and Universities in Henan Province,China(No.20A460023)。
文摘Hybrid joints have better tensile properties than pure bonded and bolted bolts,and are increasingly used in the aerospace field.Tensile tests are carried out for the Hybrid Bonded/Bolted(HBB)joints of Carbon Fiber Reinforced Polymer(CFRP)laminate and titanium alloy plate under different bolt numbers,and the corresponding load–displacement curves are obtained.At the same time,based on Continuum Damage Mechanics(CDM)theory,which is derived from 3D Hashin failure criteria,and a Cohesive Zone Model(CZM),the tensile strength prediction model of the composite laminate-titanium alloy plate multi-bolted HBB joint was established,and the numerical simulation results were in good agreement with the experimental height,which validate the feasibility of the model.The difference in the bearing capacity of HBB joints under different numbers of bolts is compared and analyzed.On this basis,the influence of inter-bolt distance on the tensile properties of the HBB joints is explored.The results show that the double-nail HBB joints can effectively improve the end warpage and low bearing capacity of the single-nail HBB joints.The tensile failure load of the double-nail HBB joints under the standard lap width(30 mm)is 82.6%higher than that of the single nail,the tensile failure load of the three-bolt HBB joints is 34.1%higher than that of the double nail.For the three-bolt HBB joint,the joint strength is controlled by the adhesive and the external bolt,while the internal bolt is redundant,the hybrid joint can be simplified by reducing the middle bolt.The inter-bolt distance has a great influence on the failure load of the hybrid joint.Increasing the inter-bolt distance can effectively improve the bearing capacity of the structure.
基金supported by grants from National Key R&D Program of China(2020YFC0848900)the Strategic Priority CAS Project(XDB38000000)Chinese Academy of Sciences and the National Major Science and Technology Project for Control and Prevention of Major Infectious Diseases in China(2018ZX10305409,2018ZX10301401,2018ZX10732401)
文摘In response to the current coronavirus disease 2019(COVID-19)pandemic,it is crucial to understand the origin,transmission,and evolution of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which relies on close surveillance of genomic diversity in clinical samples.Although the mutation at the population level had been extensively investigated,how the mutations evolve at the individual level is largely unknown.Eighteen time-series fecal samples were collected from nine patients with COVID-19 during the convalescent phase.The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method.First,we demonstrated the outstanding performance of the hybrid capture method in detecting intra-host variants.We identified 229 intra-host variants at 182 sites in 18 fecal samples.Among them,nineteen variants presented frequency changes>0.3 within 1-5 days,reflecting highly dynamic intrahost viral populations.Moreover,the evolution of the viral genome demonstrated that the virus was probably viable in the gastrointestinal tract during the convalescent period.Meanwhile,we also found that the same mutation showed a distinct pattern of frequency changes in different individuals,indicating a strong random drift.In summary,dramatic changes of the SARS-CoV-2 genome were detected in fecal samples during the convalescent period;whether the viral load in feces is sufficient to establish an infection warranted further investigation.
基金This study was supported by the National Key R&D Program of China(Grant No.2020YFC0847000)the National Natural Science Foundation of China(Grant Nos.31571370,91731302,and 31772435).
文摘A novel RNA virus,the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is responsible for the ongoing outbreak of coronavirus disease 2019(COVID-19).Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19.However,due to extensive sampling bias and existence of infection clusters during the epidemic spread,direct applications of existing approaches can lead to biased parameter estimations and data misinterpretation.In this study,we first present robust estimator for the time to the most recent common ancestor(TMRCA)and the mutation rate,and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2.The mutation rate is inferred to be 8.69×10^(−4) per site per year with a 95%confidence interval(CI)of[8.61×10^(−4),8.77×10^(−4)],and the TMRCA of the samples inferred to be Nov 28,2019 with a 95%CI of[Oct 20,2019,Dec 9,2019].The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market.We further demonstrate that genetic polymorphism patterns,including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters,are similar to those caused by evolutionary forces such as natural selection.Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism of SARS-CoV-2.Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081.
文摘In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive.By the blind watchmaker argument,such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.
基金supported by the National Key R&D Program of China(No.2017YFA0303800)the National Natural Science Foundation of China(Nos.61575162,11874300,11634010,61675169,and61505165)
文摘We demonstrate an all-fiber Q-switched cylindrical vector laser based on a black phosphorus saturable absorber and a transverse mode converter. The saturable absorber is prepared by incorporating the polyvinyl alcohol with anti-oxidized black phosphorus nanosheets exfoliated in aqueous poly(dimethyldiallyl ammonium chloride)solution. The mode converter is composed of a tapered two-mode fiber and a single-mode fiber, and it can excite switchable azimuthally and radially polarized beams by modulating the input polarization. By enhancing the pump power from 64.68 to 174.82 mW, the repetition rate of the Q-switched azimuthally/radially polarized laser enlarges from 16.72/19.25 to 30.71/37.82 kHz.
基金supported by CAMS Innovation Fund for Medical Sciences(2016-I2M-1-014,2017-I2M-3-017)the National Major Science&Technology Project for Control and Prevention of Major Infectious Diseases in China(2017ZX10103004,2018ZX10305409,2018ZX10301401,2018ZX10732401)Fondation Mérieux.The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘The surveillance and prevention of pathogenic microbiological contamination are the most important tasks of biosafety management in the lab.There is an urgent need to establish an effective and unbiased method to evaluate and monitor such contamination.This study aims to investigate the utility of next generation sequencing(NGS)method to detect possible contamination in the microbiology laboratory.Environmental samples were taken at multiple sites at the lab including the inner site of centrifuge rotor,the bench used for molecular biological tests,the benches of biosafety cabinets used for viral culture,clinical sample pre-treatment and nucleic acids extraction,by scrubbing the sites using sterile flocked swabs.The extracted total nucleic acids were used to construct the libraries for deep sequencing according to the protocol of Ion Torrent platform.At least 1G raw data was obtained for each sample.The reads of viruses and bacteria accounted for 0.01±0.02%,and 77.76±12.53%of total reads respectively.The viral sequences were likely to be derived from gene amplification products,the nucleic acids contaminated in fetal bovine serum.Reads from environmental microorganisms were also identified.Our results suggested that NGS method was capable of monitoring the nucleic acids contaminations from different sources in the lab,demonstrating its promising utility in monitoring and assessing the risk of potential laboratory contamination.The risk of contamination from reagents,remnant DNA and environment should be considered in data analysis and results interpretation.
基金The Science and Technology Commission of Shanghai MunicipalityShenzhen Science and Technology Program(2023A1515012285)+4 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(XDB35030101)Fundamental Research Funds for the Central Universities(23GH030508)Mathematical Basic Science Research Project of Shaanxi(22JSQ039)NaturalScience Basic Research Program of Shaanxi Province(2023-JCYB-502)National Natural Science Foundation of China(62275236,62305270)。
文摘Mid-infrared frequency-comb spectroscopy enables measurement of molecules at megahertz spectral resolution,sub-hertz frequency accuracy,and microsecond acquisition speed.However,the widespread adoption of this technique has been hindered by the complexity and alignment sensitivity of mid-infrared frequency-comb sources.Leveraging the underexplored mid-infrared window of silica fibers presents a promising approach to address these challenges.In this study,we present the first,to the best of our knowledge,experimental demonstration and quantitative numerical description of mid-infrared frequency-comb generation in silica fibers.Our all-silica-fiber frequency comb spans over two octaves(0.8μm to 3.4μm)with a power output of 100 mW in the mid-infrared region.The amplified quantum noise is suppressed using four-cycle(25 fs)driving pulses,with the carrier-envelope offset frequency exhibiting a signal-to-noise ratio of 40 dB and a free-running bandwidth of 90 kHz.Our developed model provides quantitative guidelines for mid-infrared frequency-comb generation in silica fibers,enabling all-fiber frequency-comb spectroscopy in diverse fields such as organic synthesis,pharmacokinetics processes,and environmental monitoring.
基金supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2019PT310029)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2023-I2M-2-001)+3 种基金the National Natural Science Foundation of China(82161148009)the Fundamental Research Funds for the Central Universities(3332021092)the Strategic Priority Research Program of Chinese Academy of Sciences(grant no.XDB38030400)the Key Collaborative Research Program of the Alliance of International Science Organizations(ANSO-CR-KP-2022-09).
文摘The gut microbiota undergoes substantial changes in COVID-19 patients;yet,the utility of these alterations as prognostic biomarkers at the time of hospital admission,and its correlation with immunological and hematological parameters,remains unclear.The objective of this study is to investigate the gut microbiota's dynamic change in critically ill patients with COVID-19 and evaluate its predictive capability for clinical outcomes alongside immunological and hematological parameters.In this study,anal swabs were consecutively collected from 192 COVID-19 patients(583 samples)upon hospital admission for metagenome sequencing.Simultaneously,blood samples were obtained to measure the concentrations of 27 cytokines and chemokines,along with hematological and biochemical indicators.Our findings indicate a significant correlation between the composition and dynamics of gut microbiota with disease severity and mortality in COVID-19 patients.Recovered patients exhibited a higher abundance of Veillonella and denser interactions among gut commensal bacteria compared to deceased patients.Furthermore,the abundance of gut commensal bacteria exhibited a negative correlation with the concentration of proinflammatory cytokines and organ damage markers.The gut microbiota upon admission showed moderate prognostic prediction ability with an AUC of 0.78,which was less effective compared to predictions based on immunological and hematological parameters(AUC 0.80 and 0.88,respectively).Noteworthy,the integration of these three datasets yielded a higher predictive accuracy(AUC 0.93).Our findings suggest the gut microbiota as an informative biomarker for COVID-19 prognosis,augmenting existing immune and hematological indicators.
基金National Natural Science Foundation of China(NSFC)(61575162,61405161,11404263,61675169)Natural Science Foundation of Shannxi Province(2015JQ6211)
文摘We demonstrate that ferroferric-oxide(Fe_3O_4) nanoparticles exhibit nonlinear saturable absorption property at1.55 μm, and fabricate two filmy saturable absorbers by embedding the nanoparticles into a polyvinyl alcohol(PVA) film or polyimide(PI) film separately. In the Fe_3O_4-PVA(Fe_3O_4-PI) Q-switched fiber laser, the pulse repetition rate increases from 8.5 kHz(5.5 kHz) to 28 kHz(49 kHz) and the pulse duration decreases from 23.5 μs(47 μs) to 6 μs(3.5 μs) by varying the pump power from 25 m W(23 mW) to 150 m W(650 mW). Experiment results indicate that PI-based saturable absorbers can afford larger powers than PVA-based saturable absorbers, which can be attributed to the higher fusion point of the PI film. The Fe_3O_4-PI saturable absorber exhibits features of high damage threshold, low cost, and good flexibility, which could be applied in fields of near-infrared pulse generation and frequency conversions.
基金funded by the National Natural Science Foundation of China(Grant No.82161148009)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB38030400)+2 种基金the Capital Health Development and Research Special Programme(Grant No.20211G-3012)the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico(CNPq)-NGS-BRICS-n°:440931/2020-7the Russian Foundation for Basic Research(RFBR)(Grant No.20-54-80014)。
文摘A new variant of concern for SARS-CoV-2,Omicron(B.1.1.529),was designated by the World Health Organization on November 26,2021.This study analyzed the viral genome sequencing data of 108 samples collected from patients infected with Omicron.First,we found that the enrichment efficiency of viral nucleic acids was reduced due to mutations in the region where the primers anneal to.Second,the Omicron variant possesses an excessive number of mutations compared to other variants circulating at the same time(median:62 vs.45),especially in the Spike gene.Mutations in the Spike gene confer alterations in 32 amino acid residues,more than those observed in other SARS-CoV-2 variants.Moreover,a large number of nonsynonymous mutations occur in the codons for the amino acid residues located on the surface of the Spike protein,which could potentially affect the replication,infectivity,and antigenicity of SARS-CoV-2.Third,there are 53 mutations between the Omicron variant and its closest sequences available in public databases.Many of these mutations were rarely observed in public databases and had a low mutation rate.In addition,the linkage disequilibrium between these mutations was low,with a limited number of mutations concurrently observed in the same genome,suggesting that the Omicron variant would be in a different evolutionary branch from the currently prevalent variants.To improve our ability to detect and track the source of new variants rapidly,it is imperative to further strengthen genomic surveillance and data sharing globally in a timely manner.
基金supported by grants from the National Key R&D Program of China(Grant Nos.2021YFC0863300,2020YFC0848900,and 2016YFE0206600)the National Natural Science Foundation of China(Grant No.82161148009)+3 种基金the Strategic Priority Research Program of Chinese Academy of Sciences,China(Grant Nos.XDA19090116 and XDB38060100)the Open Biodiversity and Health Big Data Programme of International Union of Biological Sciences,International Partnership Program of Chinese Academy of Sciences(Grant No.153F11KYSB20160008)the Professional Association of the Alliance of International Science Organizations(Grant No.ANSO-PA-2020-07)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2017141)。
文摘COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF1ab)of this cluster.Furthermore,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introductions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.
基金supported by the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDA17010201)the National Natural Science Foundation of China(Grant No.41621004)the Key Research Program of the Institute of Geology&Geophysics,CAS(Grant No.IGGCAS-201904)。
文摘As the globe has witnessed the pandemic,epidemic diseases exert a strong impact on human beings and ecosystems.Since the Sun is the primary energy source of the Earth,some scientific pioneers attempted to search for the discernible relation between solar activity and the incidence of epidemics.In this study,the periodic changes and trends of ancient Chinese epidemic data were analyzed in comparison with those of sunspot numbers,a solar activity proxy.The results show that the epidemic and solar activity changes are in good agreement to a certain extent,especially during the Gleissberg and the de Vries cycles.The wavelet coherence shows that the frequency of the epidemic data and sunspot numbers are highly associated.In addition,results from the ensemble empirical mode decomposition illustrate consistent variations in low-frequency decompositions.This study has important implications for further understanding of the potential impact of solar activity on Earth’s biosphere,the underlying mechanism of which needs further exploration.
文摘In recent decades,emerging and re-emerging human-infecting pathogens have been represented as huge threats to public health and have become a global concern(1).After outbreaks of two coronaviruses(CoVs),severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV),severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)became the first-known pandemic hastening CoV with tremendous wrecking to the world(2).The origin tracing of these emerging pathogens is of great significance in infectious disease prevention and control(3–4).The origin of SARS-CoV-2 remains elusive after the more than 3-year pandemic,though scientists around the world are making great efforts.From the experience of studying many other infectious pathogens,origin tracing is systematic and time-consuming work.The supposed origins of many infectious pathogens are still in debate,including SARS-CoV and human immunodeficiency virus,etc(5).
基金the National Natural Science Foundation of China(grant number 82161148009)the Non‐profit Central Research Institute Fund of the Chinese Academy of Medical Science(grant number APL211276910010201002008)+4 种基金the Shenzhen Science and Technology Innovation Commission Key project(grant number JSGG20200225152648408)the Shenzhen Key Medical Discipline Construction Fund(grant number SZXK064)the Key Project of Shenzhen Science and Technology Innovation Commission(grant number KCXFZ2020020110061900)the First Fighting the Epidemic Project of Shenzhen(grant number JSGG 20210901145004012)the key project of Beijing Natural Science Foundation(grant number Z190017).
文摘We analyzed variations in the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)genome during a flight-related cluster outbreak of coronavirus disease 2019(COVID-19)in Shenzhen,China,to explore the characteristics of SARS-CoV-2 transmission and intra-host single nucleotide variations(iSNVs)in a confined space.Thirty-three patients with COVID-19 were sampled,and 14 were resampled 3-31 days later.All 47 nasopharyngeal swabs were deep-sequenced.iSNVs and similarities in the consensus genome sequence were analyzed.Three SARS-CoV-2 variants of concern,Delta(n=31),Beta(n=1),and C.1.2(n=1),were detected among the 33 patients.The viral genome sequences from 30 Delta-positive patients had similar SNVs;14 of these patients provided two successive samples.Overall,the 47 sequenced genomes contained 164 iSNVs.Of the 14 paired(successive)samples,the second samples(T2)contained more iSNVs(median:3;95%confidence interval[95%CI]:2.77-10.22)than did the first samples(T1;median:2;95%CI:1.63-3.74;Wilcoxon test,P=0.021).38 iSNVs were detected in T1 samples,and only seven were also detectable in T2 samples.Notably,T2 samples from two of the 14 paired samples had additional mutations than the T1 samples.The iSNVs of the SARS-CoV-2 genome exhibited rapid dynamic changes during a flight-related cluster outbreak event.Intra-host diversity increased gradually with time,and new site mutations occurred in vivo without a population transmission bottleneck.Therefore,we could not determine the generational relationship from the mutation site changes alone.
