Adaptive mutations of H5 subtype avian influenza virus under the immune selection pressure in experimental conditions

doi:10.1016/j.jia.2026.04.004

Advanced Online Publication | Current Issue | Archive | Adv Search

Yurui Dong¹, Ying Bian¹, Chenzhi Huo¹, Yuwei Wu¹, Yun Du¹, Ruihan Yang¹, Tao Qin^1,^2,^3,^4,^5,⁶, Sujuan Chen^1,^2,^3,^4,^5,⁶, Hui Yang^1,^2,^3,^4,^5,⁶^#, Daxin Peng ^1,^2,^3,^4,^5,⁶^#, Xiufan Liu^1,^2,^3,^4,^5,⁶

¹ College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China

²Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou 225009, China

³Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou 225009, China

⁴ Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China

⁵Jiangsu Research Centre of Engineering and Technology for Prevention and Control of Poultry Disease, Yangzhou 225009, China

⁶Jiangsu Interdisciplinary Center for Zoonoses and Biosafety, Yangzhou University, Yangzhou 225009, China

Highlights

1. Three types of in vivo and in vitro models for selecting immune-escape mutants of H5 subtype avian influenza virus were established.

2. The HA K205N/T mutation reduced the viral HI and microneutralization titers, while the PB2 S155N mutation enhanced the viral pathogenicity in mice.

3. The PB2 S155N mutation delayed the emergence of HA K205N mutation during H5N1 immune pressure evolution.

Abstract
References

Download: PDF in ScienceDirect
Export: BibTeX | EndNote (RIS)

摘要

高致病性禽流感病毒（AIV）在传播过程中通过抗原漂移不断演化，使其能逃逸宿主免疫应答并具有跨种传播的能力，给全球养禽业造成巨大经济损失，也对公共卫生安全构成巨大挑战。为鉴定免疫选择压力下H5N1亚型AIV的适应性突变位点，本研究将SY（Re-5类似株）毒株与相应鸡抗血清混合后在SPF鸡胚和鸡胚成纤维细胞（CEF）连续传代，或将SY毒株在免疫鸡体内连续传代。对逃逸抗血清中和能力的子代病毒进行测序，在HA、PB2和PB1蛋白中共鉴定到12个氨基酸突变位点，其中HA蛋白中的K205位点存在K205T和K205N两种突变模式，二者均显著降低突变病毒与鸡抗血清的HI效价和细胞微中和效价，介导免疫逃逸作用；小鼠致病力试验显示，PB2中的K32M和E69K突变以及PB1中的M246I突变能有效减弱病毒对小鼠的致病力，而PB2中的S155N突变则通过聚合酶依赖性机制增强了病毒的复制能力，显著增强其致病力。值得注意的是，在免疫压力下，PB2中的S155N突变延迟了HA中K205N突变的出现，该现象与数据库中统计的病毒氨基酸流行趋势相一致： 2008-2011年间有一定比例PB2-S155N突变，HA-K205N突变流行率较低；而在2011年后，HA-K205N出现频率逐渐上升。综上，本研究成功建立了抗体选择压下H5N1亚型AIV适应性突变的3种模型，鉴定出免疫逃逸关键位点和哺乳动物致病力增强位点各1个，为预测新流行株的抗原漂移变异株和哺乳动物适应性突变，以及阐明H5亚型AIV表面基因与内部基因间的共进化动力学提供了一个有价值的工具。

Abstract

Highly pathogenic avian influenza viruses (AIV) primarily circulate within poultry populations. However, continuous evolution and mutation accumulation drive antigenic drift and may enable the virus to evade host immunity and cross the species barrier. To identify residues associated with antigenic changes and virulence in the H5N1 virus under immune selection pressure, SPF chickens, SPF chicken embryos, and chicken embryo fibroblast cells were used as model to serially passage the SY (Re-5 like) virus in the presence of homologous chicken antiserum. Progeny viruses escaped the neutralizing capacity of the antiserum were sequenced. A total of twelve amino acid mutation sites were identified in the HA, PB2, and PB1 proteins. The results showed that in the HA of the H5N1 virus, both K205N and K205T mutation patterns resulted in a significant reduction in HI titers and microneutralization titers when tested with chicken antisera. The K32M and E69K mutations in PB2, along with the M246I mutation in PB1 could effectively attenuate viral pathogenicity in mice, whereas the S155N mutation in PB2 significantly enhanced it. Notably, under the immune pressure, the S155N mutation in PB2 delayed the emergence of K205N substitution in HA. This in vivo and in vitro method for selecting immune-escape mutants provides a valuable tool for predicting emerging antigenic variants and mammalian adaptive mutations, as well as elucidating the co-evolution dynamics between surface and internal genes in H5N1 viruses.

Keywords: H5N1 antigenic drift co-evolution adaptive mutations immune escape

Online: 07 April 2026

Fund:

This study was supported by the National Key Research and Development Program of China (2021YFD1800202 and 2022YFD1801001), the National Natural Science Foundation of China (32373042 and 32503006), the Yangzhou University “Jie Bang Gua Shuai” project, China (YZUXK202316), Jiangsu Provincial R&D Program, China (BE2022329), the Basic Research Program of Jiangsu Province, China (BK20250929), the Natural Science Foundation of Yangzhou (YZ2025143), the China Postdoctoral Science Foundation (2025M773041), the Open Project Program of Jiangsu Key Laboratory of Zoonosis (R2502), Jiangsu Province University Outstanding Science and Technology Innovation Team Project [(2021) NO.1], and the Priority Academic Program Development of Jiangsu Higher Education (PAPD).

About author: #Correspondence Hui Yang, E-mail: huiy@yzu.edu.cn; Daxin Peng, E-mail: pengdx@yzu.edu.cn

	Service
	E-mail this article
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors

Cite this article:

Yurui Dong, Ying Bian, Chenzhi Huo, Yuwei Wu, Yun Du, Ruihan Yang, Tao Qin, Sujuan Chen, Hui Yang, Daxin Peng, Xiufan Liu. 2026. Adaptive mutations of H5 subtype avian influenza virus under the immune selection pressure in experimental conditions. Journal of Integrative Agriculture, Doi:10.1016/j.jia.2026.04.004

Biacchesi S, Skiadopoulos M H, Yang L, Murphy B R, Collins P L, Buchholz U J. 2005. Rapid human metapneumovirus microneutralization assay based on green fluorescent protein expression. Journal of Virological Methods, 128, 192-197.

Chang P, Sealy J E, Sadeyen J R, Bhat S, Lukosaityte D, Sun Y, Iqbal M. 2020. Immune Escape Adaptive Mutations in the H7N9 Avian Influenza Hemagglutinin Protein Increase Virus Replication Fitness and Decrease Pandemic Potential. Journal of Virology, 94, e00216-00220.

Chang P, Sealy J E, Sadeyen J R, Iqbal M. 2019. Amino Acid Residue 217 in the Hemagglutinin Glycoprotein Is a Key Mediator of Avian Influenza H7N9 Virus Antigenicity. Journal of Virology, 93, e01627-01618.

Chauhan R P, Gordon M L. 2022. An overview of influenza A virus genes, protein functions, and replication cycle highlighting important updates. Virus Genes, 58, 255-269.

Chu J T, Gu H, Sun W, Fan R L, Nicholls J M, Valkenburg S A, Poon L L. 2023. Heterosubtypic immune pressure accelerates emergence of influenza A virus escape phenotypes in mice. Virus Research, 323, 198991.

Cui P, Zeng X, Li X, Li Y, Shi J, Zhao C, Qu Z, Wang Y, Guo J, Gu W, Ma Q, Zhang Y, Lin W, Li M, Tian J, Wang D, Xing X, Liu Y, Pan S, Zhang Y, Bao H, Liu L, Tian G, Li C, Deng G, Chen H. 2022. Genetic and biological characteristics of the globally circulating H5N8 avian influenza viruses and the protective efficacy offered by the poultry vaccine currently used in China. Science China-Life Sciences, 65, 795-808.

Fan S, Hatta M, Kim J H, Halfmann P, Imai M, Macken C A, Le M Q, Nguyen T, Neumann G, Kawaoka Y. 2014. Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts. Nature Communications, 5, 5021.

Galli M, Giacomelli A, Lai A, Zehender G. 2025. H5N1 influenza A virus: lessons from past outbreaks and emerging threats. Infezioni in Medicina, 33, 76-89.

Gambotto A, Barratt-Boyes S M, de Jong M D, Neumann G, Kawaoka Y. 2008. Human infection with highly pathogenic H5N1 influenza virus. Lancet, 371, 1464-1475.

Gu C, Zeng X, Song Y, Li Y, Liu L, Kawaoka Y, Zhao D, Chen H. 2019. Glycosylation and an amino acid insertion in the head of hemagglutinin independently affect the antigenic properties of H5N1 avian influenza viruses. Science China-Life Sciences, 62, 76-83.

Guarnaccia T, Carolan L A, Maurer-Stroh S, Lee R T, Job E, Reading P C, Petrie S, McCaw J M, McVernon J, Hurt A C, Kelso A, Mosse J, Barr I G, Laurie K L. 2013. Antigenic drift of the pandemic 2009 A(H1N1) influenza virus in A ferret model. Plos Pathogens, 9, e1003354.

Guo Y, Bai X, Liu Z, Liang B, Zheng Y, Dankar S, Ping J. 2023. Exploring the alternative virulence determinants PB2 S155N and PA S49Y/D347G that promote mammalian adaptation of the H9N2 avian influenza virus in mice. Veterinary Research, 54, 97.

Hensley S E, Das S R, Bailey A L, Schmidt L M, Hickman H D, Jayaraman A, Viswanathan K, Raman R, Sasisekharan R, Bennink J R, Yewdell J W. 2009. Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift. Science, 326, 734-736.

Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster R G. 2000. A DNA transfection system for generation of influenza A virus from eight plasmids. Proceedings of the National Academy of Sciences of the United States of America, 97, 6108-6113.

Imai M, Kawaoka Y. 2012. The role of receptor binding specificity in interspecies transmission of influenza viruses. Current Opinion in Virology, 2, 160-167.

Jang S G, Kim Y I, Casel M A B, Choi J H, Gil J R, Rollon R, Kim E H, Kim S M, Ji H Y, Park D B, Hwang J, Ahn J W, Kim M H, Song M S, Choi Y K. 2024. HA N193D substitution in the HPAI H5N1 virus alters receptor binding affinity and enhances virulence in mammalian hosts. Emerging Microbes & Infections, 13, 2302854.

Kaverin N V, Rudneva I A, Ilyushina N A, Varich N L, Lipatov A S, Smirnov Y A, Govorkova E A, Gitelman A K, Lvov D K, Webster R G. 2002. Structure of antigenic sites on the haemagglutinin molecule of H5 avian influenza virus and phenotypic variation of escape mutants. Journal of General Virology, 83, 2497-2505.

Kok A, Wilks S H, Tureli S, James S L, Bestebroer T M, Burke D F, Funk M, van der Vliet S, Spronken M I, Rijnink W F, Pattinson D J, de Meulder, D, Rosu M E, Lexmond P, van den Brand J M A, Herfst S, Smith D J, Fouchier R A M, Richard M. 2025. A vaccine central in A(H5) influenza antigenic space confers broad immunity. Nature, 647, 1005-1013.

Kong H, Burke D F, da Silva Lopes T J, Takada K, Imai M, Zhong G, Hatta M, Fan S, Chiba S, Smith D, Neumann G, Kawaoka Y. 2021. Plasticity of the Influenza Virus H5 HA Protein. mBio, 12, e03324-03320.

Li J, Gu M, Liu K, Gao R, Sun W, Liu D, Jiang K, Zhong L, Wang X, Hu J, Hu S, Liu X, Shi W, Ren H, Peng D, Liu X. 2020. Amino acid substitutions in antigenic region B of hemagglutinin play a critical role in the antigenic drift of subclade 2.3.4.4 highly pathogenic H5NX influenza viruses. Transboundary And Emerging Diseases, 67, 263-275.

Li J, Liang L, Jiang L, Wang Q, Wen X, Zhao Y, Cui P, Zhang Y, Wang G, Li Q, Deng G, Shi J, Tian G, Zeng X, Jiang Y, Liu L, Chen H, Li C. 2021. Viral RNA-binding ability conferred by SUMOylation at PB1 K612 of influenza A virus is essential for viral pathogenesis and transmission. Plos Pathogens, 17, e1009336.

Li M, Yin X, Guan L, Zhang X, Deng G, Li T, Cui P, Ma Y, Hou Y, Shi J, Chen H. 2019. Insights from avian influenza surveillance of chickens and ducks before and after exposure to live poultry markets. Science China Life Sciences, 62, 854-857.

Liang L, Jiang L, Li J, Zhao Q, Wang J, He X, Huang S, Wang Q, Zhao Y, Wang G, Sun N, Deng G, Shi J, Tian G, Zeng X, Jiang Y, Liu L, Liu J, Chen P, Bu Z, Kawaoka Y, Chen H, Li C. 2019. Low Polymerase Activity Attributed to PA Drives the Acquisition of the PB2 E627K Mutation of H7N9 Avian Influenza Virus in Mammals. mBio, 10 (3):e01162-19.

Liu S, Zhuang Q, Wang S, Jiang W, Jin J, Peng C, Hou G, Li J, Yu J, Yu X, Liu H, Sun S, Yuan L, Chen J. 2020. Control of avian influenza in China: Strategies and lessons. Transboundary And Emerging Diseases, 67, 1463-1471.

Liu Y, Jin W, Guan W, Zeng Z, Yang Z. 2022. The genetic characterization of hemagglutinin (HA), neuraminidase (NA) and polymerase acidic (PA) genes of H3N2 influenza viruses circulated in Guangdong Province of China during 2019-2020. Virus Genes, 58, 392-402.

Luczo J M, Spackman E. 2024. Epitopes in the HA and NA of H5 and H7 avian influenza viruses that are important for antigenic drift. Fems Microbiology Reviews, 48(3):fuae014.

Moratorio G, Kesavardhana S, Lakdawala S S, Poon L, Worobey M, Nuzzo J, Su S. 2024. H5N1 influenza: Urgent questions and directions. Cell, 187, 4546-4548.

Shi J, Zeng X, Cui P, Yan C, Chen H. 2023. Alarming situation of emerging H5 and H7 avian influenza and effective control strategies. Emerging Microbes & Infections, 12, 2155072.

Shortridge K F, Zhou N N, Guan Y, Gao P, Ito T, Kawaoka Y, Kodihalli S, Krauss S, Markwell D, Murti K G, Norwood M, Senne D, Sims L, Takada A, Webster R G. 1998. Characterization of avian H5N1 influenza viruses from poultry in Hong Kong. Virology, 252, 331-342.

Smith D J, Lapedes A S, de Jong J C, Bestebroer T M, Rimmelzwaan G F, Osterhaus A D, Fouchier R A. 2004. Mapping the antigenic and genetic evolution of influenza virus. Science, 305, 371-376.

Su H, Zhao Y, Zheng L, Wang S, Shi H, Liu X. 2020. Effect of the selection pressure of vaccine antibodies on evolution of H9N2 avian influenza virus in chickens. Applied Microbiology and Biotechnology Express, 10 (1):98.

Subbarao E K, London W, Murphy B R. 1993. A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. Journal of Virology, 67, 1761-1764.

Sun H, Li H, Tong Q, Han Q, Liu J, Yu H, Song H, Qi J, Li J, Yang J, Lan R, Deng G, Chang H, Qu Y, Pu J, Sun Y, Lan Y, Wang D, Shi Y, Liu W J, Chang K C, Gao G F, Liu J. 2023. Airborne transmission of human-isolated avian H3N8 influenza virus between ferrets. Cell, 186, 4074-4084.e4011.

Uno N, Ebensen T, Guzman C A, Ross T M. 2024. Intranasal administration of octavalent next-generation influenza vaccine elicits protective immune responses against seasonal and pre-pandemic viruses. Journal of Virology, 98, e0035424.

Wang X, Meng F, Wang D, Liu X, Chen S, Qin T, Peng D, Liu, X. 2016. Characteristics of two highly pathogenic avian influenza H5N8 viruses with different pathogenicity in mice. Archives of Virology, 161, 3365-3374.

Wang X, Tang X E, Zheng H, Gao R, Lu X, Yang W, Zhou L, Chen Y, Gu M, Hu J, Liu X, Hu S, Liu K, Liu X. 2024. Amino acid mutations PB1-V719M and PA-N444D combined with PB2-627K contribute to the pathogenicity of H7N9 in mice. Veterinary Research, 55, 86.

Xie R, Edwards K M, Wille M, Wei X, Wong S S, Zanin M, El-Shesheny R, Ducatez M, Poon L L M, Kayali G, Webby R J, Dhanasekaran V. 2023. The episodic resurgence of highly pathogenic avian influenza H5 virus. Nature, 622, 810-817.

Xing X, Shi J, Cui P, Yan C, Zhang Y, Zhang Y, Wang C, Chen Y, Zeng X, Tian G, Liu L, Guan Y, Li C, Suzuki Y, Deng G, Chen H. 2024. Evolution and biological characterization of H5N1 influenza viruses bearing the clade 2.3.2.1 hemagglutinin gene. Emerging Microbes & Infections, 13, 2284294.

Xu C, Zhang N, Yang Y, Liang W, Zhang Y, Wang J, Suzuki Y, Wu Y, Chen Y, Yang H, Qiao C, Chen H. 2022. Immune Escape Adaptive Mutations in Hemagglutinin Are Responsible for the Antigenic Drift of Eurasian Avian-Like H1N1 Swine Influenza Viruses. Journal of Virology, 96, e0097122.

Yang H, Dong Y, Bian Y, Huo C, Wu Y, Du Y, Yang R, Ye C, Chen S, Peng D, Liu X. 2026. Dual roles of USP39 in stabilizing PB2 and orchestrating ribonucleoprotein assembly drive H5 influenza virus replication and pathogenicity. Cell Reports, 45, 117002.

Yang H, Dong Y, Bian Y, Huo C, Zhu C, Qin T, Chen S, Peng D, Liu X. 2023. The synergistic effect of residues 32T and 550L in the PA protein of H5 subtype avian influenza virus contributes to viral pathogenicity in mice. Plos Pathogens, 19, e1011489.

Yang H, Dong Y, Bian Y, Xu N, Wu Y, Yang F, Du Y, Qin T, Chen S, Peng D, Liu X. 2022. The influenza virus PB2 protein evades antiviral innate immunity by inhibiting JAK1/STAT signalling. Nature Communications, 13, 6288.

Yuen K Y, Chan P K, Peiris M, Tsang D N, Que T L, Shortridge K F, Cheung P T, To W K, Ho E T, Sung R, Cheng A F. 1998. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet, 351, 467-471.

Zeng X, Shi J, Chen H. 2024. Control of highly pathogenic avian influenza through vaccination. Journal of Integrative Agriculture, 23, 1447-1453.

Zhang N, Quan K, Lin M, Lu Z, Li Z, Yang Y, Xu N, Yang H. Zhu J, Zhang G F, Qin T, Chen S, Peng D, Liu X. 2025. Comprehensive evaluation of HA epitope modifications in H9N2 subtype avian influenza vaccines for broad cross-protection. Journal of Integrative Agriculture.

Zhang Q, Shi J, Deng G, Guo J, Zeng X, He X, Kong H, Gu C, Li X, Liu J, Wang G, Chen Y, Liu L, Liang L, Li Y, Fan J, Wang J, Li W, Guan L, Li Q, Yang H, Chen P, Jiang L, Guan Y, Xin X, Jiang Y, Tian G, Wang X, Qiao C, Li C, Bu Z, Chen H. (2013). H7N9 influenza viruses are transmissible in ferrets by respiratory droplet. Science, 341, 410-414.

Zhang X, Chen S, Yang D, Wang X, Zhu J, Peng D, Liu X. 2015. Role of stem glycans attached to haemagglutinin in the biological characteristics of H5N1 avian influenza virus. Journal of General Virology, 96, 1248-1257.

Zhang Y, Cui P, Shi J, Chen Y Zeng X, Jiang Y, Tian G, Li C, Chen H, Kong H, Deng G. 2023. Key Amino Acid Residues That Determine the Antigenic Properties of Highly Pathogenic H5 Influenza Viruses Bearing the Clade 2.3.4.4 Hemagglutinin Gene. Viruses, 15(11):2249

[1]	Shuangxi Zhang, Xinlin Wei, Hejing Shen, Qinhu Wang, Yi Qiang, Langjun Cui, Hongxing Xu, Yuyan An, Meixiang Zhang. *Simultaneously enhancing plant growth and immunity through the application of engineered Bacillus subtilis* expressing a microbial pattern**[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[2]	Jie Liu, Jie Zhang, Huijuan Yan, Tuyong Yi, Won Bo Shim, Zehua Zhou. **FvVam6 is associated with fungal development and fumonisin biosynthesis via vacuole morphology regulation in Fusarium verticillioides** [J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[3]	Saisai Wu, Shuqing Han, Jing Zhang, Guodong Cheng, Yali Wang, Kai Zhang, Mingming Han, Jianzhai Wu. Multi-scale keypoints detection and motion features extraction in dairy cows using ResNet101-ASPP network[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[4]	Yijun Wang, Jinhao Han, Tenglong Zhang, Mengjia Sun, Hongyu Ren, Cunyao Bo, Yuqing Diao, Xin Ma, Hongwei Wang, Xiaoqian Wang. *Identification and fine mapping of a major QTL, qGPC4D, for grain protein content using wheat–Aegilops* tauschii introgression lines**[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[5]	Zhenbang Zhu, Zhengqin Ye, Wenqiang Wang, Yanhua Li, Zhe Sun, Xiuling Yu, Kegong Tian, Xiangdong Li. A rescued virus from the infectious clone of a PRRSV NADC34-like strain exhibits high pathogenicity for nursery pigs[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[6]	Xin Zhang, Jidong Zhang, Yunling Peng, Xun Yu, Lirong Lu, Yadong Liu, Yang Song, Dameng Yin, Shaogeng Zhao, Hongwu Wang, Xiuliang Jin, Jun Zheng. QTL mapping of maize plant height based on a population of doubled haploid lines using UAV LiDAR high-throughput phenotyping data[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[7]	Chenyu Li, Zumuremu Tuerxun, Yang Yang, Xiaorong Li, Fengjiao Hui, Juan Li, Zhigang Liu, Guo Chen, Darun Cai, Hui Zhang, Xunji Chen, Shuangxia Jin, Bo Li. *Application of an endogenous pGhαGloA* promoter in CRISPR/Cas12a system for efficient genome editing to creat glandless cotton germplasm**[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[8]	Mengyao Zhang, Hongli Jin, Cuicui Jiao, Yuanyuan Zhang, Yujie Bai, Zhiyuan Gong, Pei Huang, Haili Zhang, Yuanyuan Li, Hualei Wang. A candidate tick-borne encephalitis virus vaccine based on virus-like particles induces specific cellular and humoral immunity in mice[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[9]	Mengsi Zhang, Mingming Yang, Xiaoxue Zhang, Shuying Li, Shuaiwu Wang, Alex Muremi Fulano, Yongting Meng, Xihui Shen, Lili Huang, Yao Wang. Two-Component Signaling System RegAB Represses Pseudomonas syringae pv. actinidiae T3SS by Directly Binding to the promoter of hrpRS[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[10]	Jiyu Zhao, Xudong Sun, Yuqi Xue, Alam Sher, Jiayu Ran, Peng Liu, Bin Zhao, Baizhao Ren, Ningning Yu, Hao Ren, Jiwang Zhang. Optimizing nitrogen management for grain yield and nitrogen use efficiency in summer maize via coordinating the N supply–demand balance[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[11]	Renxu Chang, Yuanyuan Chen, Xinyi Xu, Hongdou Jia, John Mauck, Juan J. Loor, Yehoshav A. Ben Meir, Qiushi Xu, Xudong Sun, Chuang Xu. Free fatty acids induce apoptosis in mammary epithelial cells from ketotic dairy cows via endoplasmic reticulum stress[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[12]	Yeon Ju An, Min Young Kim, Sungup Kim, Jeongeun Lee, Sang Woo Kim, Jung In Kim, Eunyoung Oh, Heungsu Lee, Kwang-Soo Cho, Seung-Hyun Kim, Myoung Hee Lee, Eunsoo Lee. *QTL mapping and allele stacking for enhanced lignan content in sesame (Sesamum* indicum L.) using genotyping-by-sequencing**[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[13]	Jingui Wei, Qiang Chai, Wen Yin, Yao Guo, Zhilong Fan, Falong Hu, Qiming Wang, Shoufa Mao. Mixed cropping green manure can simultaneously improve nutrition production and quality of spring wheat grain under reduced chemical nitrogen supply[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[14]	Ying Liu, Jiangyao Fu, Haotian Chen, Yajun Zhang, Siyu Li, Kuanyu Zhu, Yunji Xu, Weilu Wang, Junfei Gu, Hao Zhang, Zhiqin Wang, Lijun Liu, Jianhua Zhang, Weiyang Zhang, Jianchang Yang. Cytokinins redistributing drives nitrogen remobilization from source to sink in wheat under moderate water limitation during grain filling[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.
[15]	Qian Tang, Jianhong Ren, Xinru Zhang, Cai Wu, Yarong Zhang, Dahong Bian, Guangzhou Liu, Yanhong Cui, Xiong Du, Chuang Wang, Zhen Gao. Plant growth retardant increases nitrogen utilization efficiency and harvest index in maize by optimizing Plant Horizontal-Vertical Ratio and vascular bundles morphology[J]. >Journal of Integrative Agriculture, 2026, 25(5): 0-.

No Suggested Reading articles found!

Viewed

Full text

Abstract

Cited

Shared

Discussed

Cite this article:

About JIA

Editorial board

For authors