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Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

Genes & Diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei jiayu wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient protection.Intranasal immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of SARS-CoV-2.In this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA vaccine.After intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 receptors.Furthermore,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and spleen.Collectively,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine

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Elevated level of high-sensitivity cardiac troponin I as a predictor of adverse cardiovascular events in patients with heart failure with preserved ejection fraction

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Chinese Medical Journal 2023年第18期136卷 2195-2202页

作者： Hongyu Hu Jingjin Li Xin Wei Jia Zhang jiayu wang Department of Cardiovascular Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Neurocardiology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China

Background:The relationship between the elevation of cardiac troponin and the increase of mortality and hospitalization rate in patients with heart failure with reduced ejection fraction is clear.This study investigated the association between the extent of elevated levels of high-sensitivity cardiac troponin I(hs-cTnI)and the prognosis in heart failure with preserved ejection fraction patients.Methods:A retrospective cohort study consecutively enrolled 470 patients with heart failure with preserved ejection fraction from September 2014 to August 2017.According to the level of hs-cTnI,the patients were divided into the elevated level group(hs-cTnI>0.034 ng/mL in male and hs-cTnI>0.016 ng/mL in female)and the normal level group.All of the patients were followed up once every 6 months.Adverse cardiovascular events were cardiogenic death and heart failure hospitalization.Results:The mean follow-up period was 36.2±7.9 months.Cardiogenic mortality(18.6%[26/140]vs.1.5%[5/330],P<0.001)and heart failure(HF)hospitalization rate(74.3%[104/140]vs.43.6%[144/330],P<0.001)were significantly higher in the elevated level group.The Cox regression analysis showed that the elevated level of hs-cTnI was a predictor of cardiogenic death(hazard ratio[HR]:5.578,95%confidence interval[CI]:2.995-10.386,P<0.001)and HF hospitalization(HR:3.254,95%CI:2.698-3.923,P<0.001).The receiver operating characteristic curve demonstrated that a sensitivity of 72.6%and specificity of 88.8%for correct prediction of adverse cardiovascular events when a level of hs-cTnI of 0.1305 ng/mL in male and a sensitivity of 70.6%and specificity of 90.2%when a level of hs-cTnI of 0.0755 ng/mL in female were used as the cut-off value.Conclusion:Significant elevation of hs-cTnI(≥0.1305 ng/mL in male and≥0.0755 ng/mL in female)is an effective indicator of the increased risk of cardiogenic death and HF hospitalization in heart failure with preserved ejection fraction patients.

关键词： Heart failure with preserved ejection fraction High-sensitivity cardiac troponin I Cardiogenic mortality Heart failure hospitalization

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Boosting with variant-matched vaccines: an opportunity to win the race against Omicron

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2126-2127页

作者： jiayu wang Tianxia Lan Qiu Sun State Key Laboratory of Biotherapy Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center for Biotherapy610041 ChengduChina

Recently,Baoling Ying et al.published a study in Cell that investigated whether using BA.1-matched or historical mRNA vaccine as a booster could enhance the protection against Omicron infection.1 In this study,the team evaluated the anti-Omicron efficacies of these two types of vaccines as primary(two-dose)immunization series or thirddose boosters in mice,respectively(Fig.1).Many of the current outbreaks of COVID-19 around the world have been shown to be driven by the Omicron variant of SARSCoV-2.2 Although vaccination remains one of the most efficient approaches to containing the pandemic,amino acid substitutions,deletions,and insertions in the spike protein of the Omicron variant have substantially impaired the efficacy of most licensed vaccines.3 Hence,more effective vaccines or vaccination strategies against Omicron are urgently needed.

关键词： vaccines impaired al.

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Development of combined transitional pavement structure for urban tram track-road grade crossings

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Frontiers of Structural and Civil Engineering 2023年第8期17卷 1199-1210页

作者： Boshun GAO Xin XIAO jiayu wang Ligao JIANG Qing YAO Key Laboratory of Road and Traffic Engineering of Ministry of Education Tongji UniversityShanghai 201804China Shanghai Urban Construction Municipal Engineering(Group)Co. Ltd.Shanghai 200065China

The grade crossings and adjacent pavements of urban trams are generally subjected to complex load conditions and are susceptible to damage.Therefore,in this study,a novel pavement structure between tram tracks and roads constructed using polyurethane(PU)elastic concrete and ultra-high-performance concrete(UHPC),referred to as a track-road transitional pavement(TRTP),is proposed.Subsequently,its performance and feasibility are evaluated using experimental and numerical methods.First,the mechanical properties of the PU elastic concrete are evaluated.The performance of the proposed structure is investigated using a three-dimensional finite element model,where vehicleinduced dynamic and static loads are considered.The results show that PU elastic concrete and the proposed combined TRTP are applicable and functioned as intended.Additionally,the PU elastic concrete achieved sufficient performance.The recommended width of the TRTP is approximately 50 mm.Meanwhile,the application of UHPC under a PU elastic concrete layer significantly reduces vertical deformation.Results of numerical calculations confirmed the high structural performance and feasibility of the proposed TRTP.Finally,material performance standards are recommended to provide guidance for pavement design and the construction of tram-grade crossings in the future.

关键词： urban tram track grade crossing combined track-road transitional pavement polyurethane elastic concrete finite element method

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Laboratory investigation of emulsified asphalt binder modified with wood-derived nano-cellulose and nano paper-cellulose

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Frontiers of Structural and Civil Engineering 2022年第11期16卷 1474-1485页

作者： Yunge WEI jiayu wang Ruoyu LI Ling XU Feipeng XIAO Key Laboratory of Road and Traffic Engineering of Ministry of Education Tongji UniversityShanghai 200092China

Emulsified asphalt is the primary material for preventive maintenance and cold-mix paving,but its low cohesive strength and poor mechanical properties limit its wide application,even with polymer modification.In this study,Styrene-Butadiene Rubber(SBR)emulsified asphalt was modified with nano-cellulose materials,namely nano paper-cellulose(NPC)and wood-derived nano-cellulose(WDC),to improve its properties.A novel preparation method of nano-cellulose solution was developed,including blending,ultrasonic stirring,and centrifugal treatment.Four types of nano-cellulose solution(0.5%NPC,0.5%,1.0%,and 1.5%WDC by weight of water)were selected.The microscopy analysis indicated that 0.5%WDC emulsion had a smaller particle size than 1.5%WDC emulsion.The rheology test indicated that WDC modified residue improved rutting resistance with the increased solution dosage due to the cross-linking effect,but its creep-and-recovery performance was worse than that of SBR emulsion residue.The NPC modified binder had a higher rutting factor than WDC modified binder at the same dosage after short-term aging.In addition,1.0%WDC could be regarded as the optimal dosage in terms of fatigue and low-temperature performance.Furthermore,Fourier Transform Infrared Spectroscopy(FTIR)results showed that 0.5%NPC modified residue performed better in long-term aging resistance compared with 0.5%WDC modified asphalt.

关键词： nano-cellulose emulsified asphalt binder dispersion rheological properties Fourier transform infrared spectroscopy

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Omicron variant:a booster depending on infection histories

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Signal Transduction and Targeted Therapy 2023年第2期8卷 325-326页

作者： jiayu wang Tianxia Lan Yuquan Wei Yoshimasa Tanaka State Key Laboratory of Biotherapy Cancer CenterWest China HospitalSichuan University and Collaborative Innovation Center for Biotherapy610041ChengduChina Center for Medical Innovation Nagasaki University1-7-1 SakamotoNagasaki852-8588Japan

Recently,Reynold et al.published a study in Science1 showing that immune imprinting patterns might differentially influence immune responses against variants of concern(VOCs)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).They also demonstrated that infection with B.1.1.529(Omicron variant)of SARS-CoV-2 confers only partial and transient protection against itself,resulting in frequent reinfections with Omicron in short time intervals.

关键词： infection al. acute

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Reducing CO_(2)emissions from the rebalancing operation of the bike-sharing system in Beijing

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Frontiers of Engineering Management 2023年第2期10卷 262-284页

作者： Meng QIN jiayu wang Wei-Ming CHEN Ke wang Center for Energy and Environmental Policy Research Beijing Institute of TechnologyBeijing 100081China School of Management and Economics Beijing Institute of TechnologyBeijing 100081China Sustainable Development Research Institute for Economy and Society of Beijing Beijing 100081China Beijing Key Lab of Energy Economics and Environmental Management Beijing 100081China

With the development of the bike-sharing system(BSS)and the introduction of green and low carbon development,the environmental impacts of BSS had received increasing attention in recent years.However,the emissions from the rebalancing of BSS,where fossil-fueled vehicles are commonly used,are usually neglected,which goes against the idea of green travel in a sharing economy.Previous studies on the bike-sharing rebalancing problem(BRP),which is considered NP-hard,have mainly focused on algorithm innovation instead of improving the solution model,thereby hindering the application of many existing models in large-scale BRP.This study then proposes a method for optimizing the CO_(2)emissions from BRP and takes the BSS of Beijing as a demonstration.We initially analyze the spatial and temporal characteristics of BSS,especially the flow between districts,and find that each district can be independently rebalanced.Afterward,we develop a rebalancing optimization model based on a partitioning strategy to avoid deciding the number of bikes being loaded or unloaded at each parking node.We then employ the tabu search algorithm to solve the model.Results show that(i)due to over launch and lack of planning in rebalancing,the BSS in Beijing shows great potential for optimization,such as by reducing the number of vehicle routes,CO_(2)emissions,and unmet demands;(ii)the CO_(2)emissions of BSS in Beijing can be reduced by 57.5%by forming balanced parking nodes at the end of the day and decreasing the repetition of vehicle routes and the loads of vehicles;and(iii)the launch amounts of bikes in specific districts,such as Shijingshan and Mentougou,should be increased.

关键词： bike-sharing CO_(2)emissions environmental benefit partitioning strategy rebalancing problem

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Predictive biomarkers of response and survival following immunotherapy with a PD-L1 inhibitor benmelstobart(TQB2450)and antiangiogenic therapy with a VEGFR inhibitor anlotinib for pretreated advanced triple negative breast cancer

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5944-5953页

作者： Yiqun Han jiayu wang Tao Sun Quchang Ouyang Jianwen Li Jie Yuan Binghe Xu National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Liaoning Cancer Hospital&Institute ShenyangLiaoning 110042China Hunan Cancer Hospital ChangshaHunan 410013China Geneplus-Shenzhen Shenzhen 518118China

In our phase Ib trial(ClinialTrials.gov Identifier:NCT03855358),benmelstobart(TQB2450),a novel humanized IgG1 antibody against PD-L1,plus antiangiogenic multikinase inhibitor,anlotinib,demonstrated promising antitumor activities in pretreated triple negative breast cancer(TNBC)patients.We conducted explorative analyses of genomic biomarkers to explore the associations with treatment response and survival outcomes.Targeted next generation sequencing(NGS)was undertaken toward circulating tumor DNA(ctDNA)collected from peripheral blood samples prior to the start of treatment and after disease progression.A total of 31 patients received targeted NGS and functional driver mutations in 29 patients were analyzed.The most frequent mutations were TP53(72%),MLL3(28%),and PIK3CA(17%).At a blood-based tumor mutational burden(bTMB)cutoff of 6.7 mutations per megabase,patients with low bTMB showed better response to anlotinib plus TQB2450(50%vs.7%,P=0.015)and gained greater PFS benefits(7.3 vs.4.1 months,P=0.012)than those with high bTMB.At a maximum somatic allele frequency(MSAF)cutoff of 10%,a low MSAF indicated a better objective response(43%vs.20%)as well as a significantly longer median PFS(7.9 vs.2.7 months,P<0.001).Patients with both low MSAF and low bTMB showed a notably better objective response to anlotinib plus TQB2450(70%vs.11%,P<0.001)and a significantly longer median PFS(11.0 vs.2.9 months,P<0.001)than patients with other scenarios.Our findings support future studes and validation of MSAF and the combined bTMB-MSAF classification as predictive biomarkers of immune checkpoint inhibitor-based regimens in advanced TNBC patients.

关键词： PIK3CA breast cancer

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Applications and prospects of artificial intelligence in covert satellite communication: a review

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Science China(Information Sciences) 2023年第2期66卷 47-77页

作者： Kun LU Heng LIU Liang ZENG jiayu wang Zhongshan ZHANG Jianping AN School of Information and Electronics Beijing Institute of Technology School of Cyberspace Science and Technology Beijing Institute of Technology

Satellite communication has the characteristics of wide coverage and large communication capacity, and is not easily affected by land disasters. It is quite suitable as a supplement to terrestrial communication networks and has been widely used in education, navigation, emergency relief, military, etc. However,due to the openness of the channel of satellite communication systems, satellite communication signals are easily eavesdropped on by eavesdroppers. This greatly threatens the privacy and security of countries and individuals. Covert satellite communication can effectively improve the covertness of satellite communication systems and greatly reduce the probability of detection by eavesdroppers. So, it has attracted more and more attention. In addition, with the development of artificial intelligence(AI), AI has been applied in many technics of covert satellite communication, which has achieved higher reliability and stronger concealment in covert satellite communication systems. The research status of key technics in covert satellite communication is discussed in this study, and the applications of AI in covert satellite communication are shown. Finally,future research directions of covert satellite communication are looked forward to. In the future, covert satellite communication technology will be an indispensable part of satellite communication systems.

关键词： satellite communication covert communication secure communication low probability of detection (LPD) artificial intelligence (AI) machine learning (ML)

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Advances in the treatment of solid tumors in children and adolescents

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Cancer Innovation 2023年第2期2卷 131-139页

作者： Jing Tian jiayu wang Sidan Li Beijing Key Laboratory of Pediatric Hematology Oncology Key Laboratory of Major Diseases in ChildrenNational Key Discipline of Pediatrics(Capital Medical University)Ministry of EducationBeijing Children's HospitalHematology CenterNational Center for Children's HealthCapital Medical UniversityBeijingChina Department of Medical Oncology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Tumor is one of the leading causes of death in children(0 to 14-year-old)and adolescents(15 to 19-year-old)worldwide.Unlike adult tumors,childhood and adolescent tumors are unique in their type,molecular characteristics,and pathogenesis,and their treatment involves many challenges.In recent years,with the development of a large number of clinical studies,the survival rate of children and adolescents with tumors has improved significantly.The extensive research and application of optimized treatment regimens and new targeted drugs have led to new hope for the treatment of childhood and adolescent tumors.This article reviews the clinical and basic research and treatment of childhood and adolescent tumors and provides new ideas for the future development of precise treatment of childhood and adolescent tumors.

关键词： children and adolescents immune checkpoint inhibitors treatment tumor

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