Crimean-Congo hemorrhagic fever virus(CCHFV)is a highly pathogenic tick-borne virus that causes severe hemorrhagic fever with high mortality rates in humans.No licensed vaccines or efficacious antiviral therapies are ...Crimean-Congo hemorrhagic fever virus(CCHFV)is a highly pathogenic tick-borne virus that causes severe hemorrhagic fever with high mortality rates in humans.No licensed vaccines or efficacious antiviral therapies are currently available.Here,we identified seven heavy chain antibodies targeting CCHFV Gc,which consist of heavy-chain variable domain(VHH)fused to human IgG1 Fc region(VHHFc).These VHH-Fc antibodies exhibited neutralizing activity against both recombinant vesicular stomatitis virus(VSV)-vectored CCHFV pseudoviruses and CCHFV transcriptionand entry-competent virus-like particles(tecVLPs).Among these,N025 achieved the most potent pseudovirus neutralization,while N013 showed remarkable efficacy in tecVLP systems,with IC_(50) values of 22.7 ng/mL and 33.0 ng/mL,respectively.AlphaFold3 structural predictions revealed that all characterized VHH-Fc antibodies target epitopes within Domain Ⅱ of the Gc protein,with partial or complete overlap with the fusion loop region.Alanine scanning mutagenesis confirmed the functional significance of these epitopes,with N013 showing the highest binding energy change(ΔΔG=25.36 kcal/mol)and moderate competition with a known fusion loop-targeting antibody.Sequence conservation analysis across representative CCHFV strains from different genetic lineages demonstrated complete conservation of the N013 and N025 epitopes,suggesting potential for broad-spectrum neutralizing activity.Together,our findings provide a novel strategy for developing CCHFV therapeutics and identify promising antibody candidates that could inform future broad-spectrum antiviral development efforts.展开更多
This paper proposes a differential-fatness-based active disturbance rejection control(ADRC)for high-speed steering control of tracked tank systems.Firstly,a high-speed steering model is established by considering the ...This paper proposes a differential-fatness-based active disturbance rejection control(ADRC)for high-speed steering control of tracked tank systems.Firstly,a high-speed steering model is established by considering the lateral component of the centrifugal force acting on the tank on the basis of modeling and analyzing the dynamic model of the low-speed steering system.Secondly,we propose a differential-flatness ADRC approach by converting the under-actuated system to a fully driven flat one.Moreover,we prove the differential flatness of the steering system,which facilitates a two-channel ADRC development.Finally,we show that both the states of the flat system and the original under-actuated system can track the reference trajectory.On the external interference condition,the system is observed to re-track the target signal within 2 s.展开更多
基金supported by the National Natural Science Foundation of China(grant no.82522044).
文摘Crimean-Congo hemorrhagic fever virus(CCHFV)is a highly pathogenic tick-borne virus that causes severe hemorrhagic fever with high mortality rates in humans.No licensed vaccines or efficacious antiviral therapies are currently available.Here,we identified seven heavy chain antibodies targeting CCHFV Gc,which consist of heavy-chain variable domain(VHH)fused to human IgG1 Fc region(VHHFc).These VHH-Fc antibodies exhibited neutralizing activity against both recombinant vesicular stomatitis virus(VSV)-vectored CCHFV pseudoviruses and CCHFV transcriptionand entry-competent virus-like particles(tecVLPs).Among these,N025 achieved the most potent pseudovirus neutralization,while N013 showed remarkable efficacy in tecVLP systems,with IC_(50) values of 22.7 ng/mL and 33.0 ng/mL,respectively.AlphaFold3 structural predictions revealed that all characterized VHH-Fc antibodies target epitopes within Domain Ⅱ of the Gc protein,with partial or complete overlap with the fusion loop region.Alanine scanning mutagenesis confirmed the functional significance of these epitopes,with N013 showing the highest binding energy change(ΔΔG=25.36 kcal/mol)and moderate competition with a known fusion loop-targeting antibody.Sequence conservation analysis across representative CCHFV strains from different genetic lineages demonstrated complete conservation of the N013 and N025 epitopes,suggesting potential for broad-spectrum neutralizing activity.Together,our findings provide a novel strategy for developing CCHFV therapeutics and identify promising antibody candidates that could inform future broad-spectrum antiviral development efforts.
基金supported by the National Natural Science Foundation of China(62422305,62373049).
文摘This paper proposes a differential-fatness-based active disturbance rejection control(ADRC)for high-speed steering control of tracked tank systems.Firstly,a high-speed steering model is established by considering the lateral component of the centrifugal force acting on the tank on the basis of modeling and analyzing the dynamic model of the low-speed steering system.Secondly,we propose a differential-flatness ADRC approach by converting the under-actuated system to a fully driven flat one.Moreover,we prove the differential flatness of the steering system,which facilitates a two-channel ADRC development.Finally,we show that both the states of the flat system and the original under-actuated system can track the reference trajectory.On the external interference condition,the system is observed to re-track the target signal within 2 s.
