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A novel deep generative model for mRNA vaccine development: Designing 5′ UTRs with N1-methyl-pseudouridine modification

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1814-1826页

作者： Xiaoshan Tang Miaozhe Huo Yuting chen Hai Huang Shugang Qin Jiaqi Luo Zeyi Qin Xin Jiang Yongmei Liu Xing Duan Ruohan Wang lingxi chen Hao Li Na Fan Zhongshan He Xi He Bairong Shen Shuai cheng Li Xiangrong Song Institute of Systems Genetics Department of Critical Care MedicineFrontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610000China Department of Computer Science City University of Hong KongHong Kong 99907China Department of Biology Brandeis UniversityBostonMA 02453USA

Efficient translation mediated by the 5'untranslated region(5'UTR)is essential for the robust efficacy of mRNA vaccines.However,the N1-methyl-pseudouridine(m1)modification of mRNA can impact the translation efficiency of the 5'UTR.We discovered that the optimal 5'UTR for m1y-modified mRNA(m1y-5'UTR)differs significantly from its unmodified counterpart,high-lighting the need for a specialized tool for designing mly-5'UTRs rather than directly utilizing high-expression endogenous gene 5'UTRs.In response,we developed a novel machine learning-based tool,Smart5UTR,which employs a deep generative model to identify superior m1y-5'UTRs in silico.The tailored loss function and network architecture enable Smart5UTR to overcome limitations inherent in existing models.As a result,Smart5UTR can successfully design superior 5'UTRs,greatly benefiting mRNA vaccine development.Notably,Smart5UTR-designed superior 5'UTRs significantly enhanced antibody titers induced by COVID-19 mRNA vaccines against the Delta and Omicron variants of SARS-CoV-2,surpassing the performance of vaccines using high-expression endogenous gene 5'UTRs.

关键词： mRNA vaccine Machine learning 5'UTR mRNA design Sequence design N1-Methyl-pseudouridine COVID-19 SARS-CoV-2

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Geographical origin identification of winter jujube(Ziziphus jujuba Dongzao')by using multi-element fingerprinting with chemometrics

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Journal of Integrative Agriculture 2024年第5期23卷 1749-1762页

作者： Xiabing Kong Qiusheng chen Min Xu Yihui Liu Xiaoming Li lingxi Han Qiang Zhang Haoliang Wan Lu Liu Xubo Zhao Jiyun Nie College of Horticulture Qingdao Agricultural University/Laboratory of Quality&Safety Risk Assessment for Fruit(Qingdao)Ministry of Agriculture and Rural Affairs/National Technology Centre for Whole Process Quality Control of FSEN Horticultural Products(Qingdao)/Qingdao Key Lab of Modern Agriculture Quality and Safety EngineeringQingdao 266109China Institute of Agricultural Product Quality Safety and NutritionTianjin Academy of Agricultural SciencesTianjin 300381China College of Food Science and Engineering Northwest A&F UniversityYangling 712100China

Winter jujube(Ziziphus jujuba'Dongzao')is greatly appreciated by consumers for its excellent quality,but brand infringement frequently occurs in the market.Here,we first determined a total of 38 elements in 167 winter jujube samples from the main winter jujube producing areas of China by inductively coupled plasma mass spectrometer(ICP-MS).As a result,16 elements(Mg,K,Mn,Cu,Zn,Mo,Ba,Be,As,Se,Cd,Sb,Ce,Er,Tl,and Pb)exhibited significant differences in samples from different producing areas.Supervised linear discriminant analysis(LDA)and orthogonal projection to latent structures discriminant analysis(OPLS-DA)showed better performance in identifying the origin of samples than unsupervised principal component analysis(PCA).LDA and OPLS-DA had a mean identification accuracy of 87.84 and 94.64%in the testing set,respectively.By using the multilayer perceptron(MLP)and C5.0,the prediction accuracy of the models could reach 96.36 and 91.06%,respectively.Based on the above four chemometric methods,Cd,Tl,Mo and Se were selected as the main variables and principal markers for the origin identification of winter jujube.Overall,this study demonstrates that it is practical and precise to identify the origin of winter jujube through multi-element fingerprint analysis with chemometrics,and may also provide reference for establishing the origin traceability system of other fruits.

关键词： winter jujube multi-element fingerprint analysis chemometrics origin traceability

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Alterations in nutrient digestion and utilization associated with different residual feed intake in Hu sheep

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Animal Nutrition 2023年第2期13卷 334-341页

作者： Hongbo Zeng Yuyang Yin lingxi chen Zhuoxin Xu Yang Luo Qian Wang Bin Yang Jiakun Wang Institute of Dairy Science College of Animal SciencesZhejiang UniversityHangzhou310058China b MoE Key Laboratory of Molecular Animal Nutrition Zhejiang UniversityHangzhou310058China School of Biological and Chemical Engineering Zhejiang University of Science and TechnologyHangzhou310023ZhejiangChina Huzhou Academy of Agricultural Sciences Huzhou313000China Hunan Institute of Animal and Veterinary Science Changsha410131China

Improving feed efficiency is crucial to the animal industry.Residual feed intake(RFI)is now regarded as an index of feed efficiency evaluation and is independent of growth characteristics.Our study aims to explore the alterations in growth performance and nutrient digestion in Hu sheep with different RFI phenotypes.Sixty-four male Hu sheep(body weight=24.39±1.12 kg;postnatal days=90±7.9)were selected for the study.After an evaluation period of 56 days and power analysis,samples were collected from 14 low RFI(L-RFI group,power=0.95)and 14 high RFI sheep(H-RFI group,power=0.95).The L-RFI sheep yielded a lower(P0.05).The acid detergent fiber,neutral detergent fiber,organic matter,and crude protein apparent digestibility were higher(P0.05)was found in urine N output(%of N intake)between the 2 groups.Furthermore,L-RFI sheep gave lower(P<0.05)serum glucose concentrations and higher(P<0.05)non-esterified fatty acid concentrations.Meanwhile,a lower ruminal acetate molar proportion(P<0.05)and higher propionate molar proportion(P<0.05)were observed in L-RFI sheep.In summary,these results revealed that despite having lower dry matter intake,L-RFI sheep possess higher nutrient digestibility,N retention,ruminal propionate production and serum glucose utilization,in order to meet energy demands.Selection for low RFI sheep could reduce feed costs,which in turn provides economic benefits to the sheep industry.

关键词： Residual feed intake Growth performance Apparent digestibility Nitrogen metabolism Rumen fermentation Sheep

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Atomically Dispersed Ruthenium Catalysts with Open Hollow Structure for Lithium-Oxygen Batteries

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Nano-Micro Letters 2024年第2期16卷 154-164页

作者： Xin chen Yu Zhang Chang chen Huinan Li Yuran Lin Ke Yu Caiyun Nan chen chen Beijing Advanced Innovation Center for Materials Genome Engineering Institute of Solid State ChemistryUniversity of Science and Technology BeijingBeijing 100083People’s Republic of China Engineering Research Center of Advanced Rare Earth Materials Department of ChemistryTsinghua UniversityBeijing 100084People’s Republic of China Beijing Key Laboratory of Energy Conversion and Storage Materials Institution College of ChemistryBeijing Normal UniversityBeijing 100875People’s Republic of China

Lithium–oxygen battery with ultrahigh theoretical energy density is considered a highly competitive next-generation energy storage device,but its practical application is severely hindered by issues such as difficult decomposition of discharge products at present.Here,we have developed N-doped carbon anchored atomically dispersed Ru sites cathode catalyst with open hollow structure(h-RuNC)for Lithium–oxygen battery.On one hand,the abundance of atomically dispersed Ru sites can effectively catalyze the formation and decomposition of discharge products,thereby greatly enhancing the redox kinetics.On the other hand,the open hollow structure not only enhances the mass activity of atomically dispersed Ru sites but also improves the diffusion efficiency of catalytic molecules.Therefore,the excellent activity from atomically dispersed Ru sites and the enhanced diffusion from open hollow structure respectively improve the redox kinetics and cycling stability,ultimately achieving a high-performance lithium–oxygen battery.

关键词： Atomically dispersed Open hollow structure Discharge product Lithium Oxygen battery

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Advances in the application of hydrogel-based scaffolds for tendon repair

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Genes & Diseases 2024年第4期11卷 296-313页

作者： Renqiang chen Fanglin chen Kenian chen Jian Xu Department of Orthopedics The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China Department of Orthopedics The Fourth Affiliated Hospital of Guangxi Medical UniversityLiuzhou Guangxi 545005China

Tendon injuries often lead to joint dysfunction due to the limited self-regeneration capacity of tendons.Repairing tendons is a major challenge for surgeons and imposes a signif-icant financial burden on society.Therefore,there is an urgent need to develop effective stra-tegies for repairing injured tendons.Tendon tissue engineering using hydrogels has emerged as a promising approach that has attracted considerable interest.Hydrogels possess excellent biocompatibility and biodegradability,enabling them to create an extracellular matrix-like growth environment for cells.They can also serve as a carrier for cells or other substances to accelerate tendon repair.In the past decade,numerous studies have made significant prog-ress in the preparation of hydrogel scaffolds for tendon healing.This review aims to provide an overview of recent research on the materials of hydrogel-based scaffolds used for tendon tis-sue engineering and discusses the delivery systems based on them.

关键词： Application Hydrogel-based Repairscaffolds Review Tendon injury Tissue engineering

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Photodegradation of xylene isomers:Kinetics,mechanism,secondary pollutant formation potential and health risk evaluation

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Journal of Environmental Sciences 2024年第2期136卷 658-669页

作者： Xiaoyan chen Weikun Zhu Sufen Feng Jiangyao chen Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control Guangdong Technology Research Center for Photocatalytic Technology Integration and Equipment EngineeringInstitute of Environmental Health and Pollution ControlGuangdong University of TechnologyGuangzhou 510006China Guangzhou Key Laboratory of Environmental Catalysis and Pollution Control Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and HealthSchool of Environmental Science and EngineeringGuangdong University of TechnologyGuangzhou 510006China

Photodegradation technology has been widely applied in the purification of industrial aromatic hydrocarbons.However,whether this technology efficiently removes the pollutants to prevent secondary pollution and health risk is still unclear.Here,the photodegradation processes of three xylenes were compared under designed reaction atmospheres and light sources.Xe lamp showed poor photodegradation ability toward xylenes,no matter in N_(2) or N_(2)+O_(2)system,while much higher photodegradation performance of xylenes were obtained under ultraviolet(UV)and vacuum ultraviolet(VUV)irradiation,especially in N_(2)+O_(2)+VUV system,where 97.9%of m-xylene,99.0%of o-xylene or 87.5%of p-xylene with the initial concentration of 860 mg/m^(3) was removed within 240 min.The xylenes underwent three processes of photo-isomerization,photodecomposition and photo-oxidation to produce intermediates of aromatics,alkanes and carbonyls.Among them,the photo-isomerization products showed the highest concentration percentage(e.g.,≥50%in o-xylene system),confirming that photo-isomerization reaction was the dominated photodegradation process of xylenes.Moreover,these isomerized products not only contributed about 97%and91%to the formation potential of O3(OFP)and secondary organic aerosols(SOAFP),but also displayed obvious non-carcinogenic risk,although one of photodecomposition product—benzene showed the highest occupational exposure risk.Therefore,the secondary pollution and health risks of photodegradation products of xylenes were non-ignorable,although the OFP,SOAFP and health risks of the generated products reduced at least 4.5 times in comparison with that of the degraded xylenes.The findings are helpful for the appropriate application of this technology in the purification of industrial organic waste gas.

关键词： Isomer aromatics Photodegradation Ozone formation Secondary organic aerosols Health risk

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Automation 5.0:The Key to Systems Intelligence and Industry 5.0

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IEEE/CAA Journal of Automatica Sinica 2024年第8期 1723-1727页

作者： Ljubo Vlacic Hailong Huang Mariagrazia Dotoli Yutong Wang Petros A.Ioannou Lili Fan Xingxia Wang Raffaele Carli chen Lv lingxi Li Xiaoxiang Na Qing-Long Han Fei-Yue Wang the Beijing Huairou Academy of Parallel Sensing the School of Mechanical and Aerospace Engineering Nanyang Technological University the Department of Electrical and Computer Engineering Purdue School of Engineering and Technology Indiana University-Purdue University Indianapolis the Department of Engineering University of Cambridge the School of Science Computing and Engineering Technologies Swinburne University of Technology the State Key Laboratory for Management and Control of Complex Systems Chinese Academy of Sciences the Dazhou Artificial Intelligence Institute the Faculty of Innovation Engineering Macau University of Science and Technology IEEE the Institute of Intelligent and Integrated Systems and the School of Engineering and Built Environment Griffith University the Department of Aeronautical and Aviation Engineering The Hong Kong Polytechnic University the Department of Electrical and Information Engineering Polytechnic of Bari the State Key Laboratory of Multimodal Artificial Intelligence Systems Institute of Automation Chinese Academy of Sciences the Qingdao Academy of Intelligent Industries the Department of Electrical Engineering-Systems University of Southern California the School of Automation Beijing Institute of Technology the School of Artificial Intelligence University of Chinese Academy of Sciences

AUTOMATION has come a long way since the early days of mechanization, i.e., the process of working exclusively by hand or using animals to work with machinery. The rise of steam engines and water wheels represented the first generation of industry, which is now called Industry 1.0. Subsequently, Industry 2.0 witnessed the development of electric power and assembly lines.

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Isotopic characteristics and source analysis of atmospheric ammonia during agricultural periods in the Xichuan area of the Danjiangkou Reservoir

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Journal of Environmental Sciences 2024年第2期136卷 460-469页

作者： Xiaoshu chen Tongqian Zhao Chunyan Xiao Xiaoming Guo Feihong chen Institute of Resources and Environment Henan Polytechnic UniversityJiaozuo 454000China

Nitrogen deposition is an important means of exogenous nitrogen input in reservoir water.Agricultural activities around the reservoir lead to a sharp increase in the concentration of ammonia in the atmosphere,which poses a threat to the reservoir water body.Clarifying the contribution of agricultural ammonia release to atmospheric NH_(x)(gaseous NH_(3)and particulate NH_(4)^(+)),in the reservoir area can provide a theoretical foundation for local reactive nitrogen control.We collected atmospheric NH_(3)and NH_(4)^(+)samples during the agricultural periods and analyzed the isotopic characteristics of atmospheric NH_(x)and the contribution rates of different ammonia sources in the Xichuan area of the Danjiangkou Reservoir.The results showed that the initialδ~(15)N values of NH_(3)(-30.0‰to–7.2‰)and particulate NH_(4)^(+)(–33‰to+4.9‰for finer and coarser particles,respectively)are different,and their contribution ratios from dissimilar ammonia sources are also different,among which NH_(4)^(+)is more susceptible to meteorological factors.However,since the atmospheric NH_(x)in the Xichuan area is mainly gaseous NH_(3),the final sources of atmospheric ammonia nitrogen source depend on gaseous NH_(3).Agricultural sources(59%-74%)were the main NH_(3)sources in this area.Among them,the fertilizer use emission was dominant;it had the highest contribution rate in summer during the agricultural period and a more prominent impact in areas with less human interference.Reasonable regulation of the application of high-ammonia releasing fertilizer,especially during the agricultural period in summer,is an effective way to reduce the threat of atmospheric ammonia to water health.

关键词： Danjiangkou reservoir Atmospheric ammonia nitrogen Isotope Ammonia source analysis Agricultural sources

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Meridional deflection of global eddy propagation derived from tandem altimetry: Mechanism and implication

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Science China Earth Sciences 2024年第3期67卷 811-825页

作者： Ge chen Xiaoyan chen Frontiers Science Center for Deep Ocean Multispheres and Earth System School of Marine TechnologyOcean University of ChinaQindao 266100China Laboratory for Regional Oceanography and Numerical Modeling Laoshan LaboratoryQindao 266237China

A common view on meridional deflection of eddy propagation is poleward for cyclones and equatorward for anticyclones. This widely accepted polarity-sensitive pattern has been increasingly undermined given that it is systematically violated on both zonal and regional scales as recently reported. Here, we approach the problem by exploring these violations in terms of eddy effects of spatiotemporal geostrophy, thermal fading, and flow dragging, yielding the following main conclusions.(1) The polarity-dependent deflection discrepancy is a pseudo feature resulting from a biased fit to the normalized eddy tracks which are spatially asymmetric(though azimuthally symmetric) between the two signs;Instead, the primary pattern of eddy deflection appears to be geographically correlated and polarity independent.(2) Geostrophic adjustment plays a critical role in defining the meridional movement of an eddy. Specifically, a consistent poleward(equatorward) trajectory bending of spatially(temporally) ageostrophic eddies is observed irrespective of their polarity.(3) The mechanism of eddy deflection is also determined by its zonal propagation direction. Westward propagating eddies are substantially affected by thermal fading, while opposite ones by flow dragging. A realistic and comprehensive understanding of eddy deflection mechanisms serves as a significant contribution to the prediction of eddy trajectory, and the protection of ocean environment.

关键词： Mesoscale eddies Eddy propagation Eddy meridional deflection Satellite observation Geostrophic adjustment

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A refined representation method of the particle size distribution curve based on grading entropy

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Particuology 2024年第5期88卷 302-311页

作者： Xing Li Qun chen Zhaozhao Liu cheng Zhou chen Wang chen chen State Key Laboratory of Hydraulics and Mountain River Engineering College of Water Resource and HydropowerSichuan UniversityChengdu610065China

The particle size distribution(PSD)curve is an important expression of the basic properties of the soil.The characteristic parameters such as median particle size D 50,effective particle size D 10,and some combinations of characteristic parameters can only represent some points of the PSD curve,failing to represent all information of the PSD curve.In this paper,a fraction characteristic parameter F that could reflect the fraction size variation of the PSD curve was introduced based on grading entropy.And a new presentation method of the A-B-F three parameters was proposed for a refined representation of the PSD curve.It was found that the newly constructed model not only better represents the differences in the width of PSD curves but also has a higher sensitivity than the A-B two-parameter model proposed by Lőrincz.For PSD curves with similar distributions,the new presentation method has a higher degree of discrimination than that of the D 50-C u-C c three-parameter or the four-parameter combination G c proposed by Arshad.Finally,the application of this new method in describing the spatial nonuniformity distribution of depositions and predicting the soil hydraulic conductivity was discussed.The research results can provide a reference for the refined representation of PSD curves.

关键词： Grading entropy Particle size distribution curve Refined representation

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