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Modularized viromimetic polymer nanoparticle vaccines(VPNVaxs) to elicit durable and effective humoral immune responses

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National Science Review 2024年第3期11卷 200-214页

作者： Zichao Huang Xinyu Zhuang Liping Liu Jiayu Zhao Sheng Ma Xinghui Si Zhenyi Zhu Fan Wu Ningyi Jin Mingyao Tian Wantong Song Xuesi Chen Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of Sciences School of Applied Chemistry and Engineering University of Science and Technology of China changchun veterinary research institute Chinese Academy of Agricultural Sciences Jilin Biomedical Polymers Engineering Laboratory State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences

Virus-like particle(VLP) vaccines had shown great potential during the COVID-19 pandemic, and was thought to be the next generation of antiviral vaccine technology due to viromimetic structures. However,the time-consuming and complicated processes in establishing a current recombinant-protein–based VLP vaccine has limited its quick launch to the out-bursting pandemic. To simplify and optimize VLP vaccine design, we herein report a kind of viromimetic polymer nanoparticle vaccine(VPNVax), with subunit receptor-binding domain(RBD) proteins conjugated to the surface of polyethylene glycol-b-polylactic acid(PEG-b-PLA) nanoparticles for vaccination against SARS-CoV-2. The preparation of VPNVax based on synthetic polymer particle and chemical post-conjugation makes it possible to rapidly replace the antigens and construct matched vaccines at the emergence of different viruses. Using this modular preparation system, we identified that VPNVax with surface protein coverage of 20%–25% had the best immunostimulatory activity, which could keep high levels of specific antibody titers over 5 months and induce virus neutralizing activity when combined with an aluminum adjuvant. Moreover, the polymer nano-vectors could be armed with more immune-adjuvant functions by loading immunostimulant agents or chemical chirality design. This VPNVax platform provides a novel kind of rapidly producing and efficient vaccine against different variants of SARS-CoV-2 as well as other viral pandemics.

关键词： vaccine polymer nanomaterials SARS-CoV-2

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M6PR interacts with the HA2 subunit of influenza A virus to facilitate the fusion of viral and endosomal membranes

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Science China(Life sciences) 2024年第3期67卷 579-595页

作者： Yuzhen Hu Li Jiang Guangwen Wang Yangming Song Zhibo Shan Xuyuan Wang Guohua Deng Jianzhong Shi Guobin Tian Xianying Zeng Liling Liu Hualan Chen Chengjun Li State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

Influenza A virus(IAV) commandeers numerous host cellular factors for successful replication. However, very few host factors have been revealed to be involved in the fusion of viral envelope and late endosomal membranes. In this study, we identified cation-dependent mannose-6-phosphate receptor(M6PR) as a crucial host factor for the replication of IAV. We found that siRNA knockdown of M6PR expression significantly reduced the growth titers of different subtypes of IAV, and that the inhibitory effect of M6PR siRNA treatment on IAV growth was overcome by the complement of exogenously expressed M6PR. When A549 cells were treated with siRNA targeting M6PR,the nuclear accumulation of viral nucleoprotein(NP) was dramatically inhibited at early timepoints post-infection, indicating that M6PR engages in the early stage of the IAV replication cycle. By investigating the role of M6PR in the individual entry and post-entry steps of IAV replication, we found that the downregulation of M6PR expression had no effect on attachment, internalization, early endosome trafficking,or late endosome acidification. However, we found that M6PR expression was critical for the fusion of viral envelope and late endosomal membranes. Of note, M6PR interacted with the hemagglutinin(HA) protein of IAV, and further studies showed that the lumenal domain of M6PR and the ectodomain of HA2 mediated the interaction and directly promoted the fusion of the viral and late endosomal membranes,thereby facilitating IAV replication. Together, our findings highlight the importance of the M6PR–HA interaction in the fusion of viral and late endosomal membranes during IAV replication.

关键词： influenza A virus M6PR HA membrane fusion late endosome

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Molecular characterization of an outbreak-involved Bacillus anthracis strain confirms the spillover of anthrax from West Africa

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Infectious Diseases of Poverty 2024年第1期13卷 93-94页

作者： Shuchao Wang Roland Suluku Mohamed B.Jalloh Ahmed F.Samba Baogui Jiang Yubiao Xie Doris Harding Mengyao Zhang Foday Sahr Mahmud E.Sesay James S.Squire Mohamed A.Vandi Moinina N.Kallon Shoufeng Zhang Rongliang Hu Yuee Zhao Zhiqiang Mi changchun veterinary research institute Chinese Academy of Agricultural Sciences Changchun China Department of Animal sciences School of Agriculture and Food Sciences Njala University Njala Sierra Leone Department of Microbiology College of Medicine and Allied Health Sciences University of Sierra Leone Freetown Sierra Leone Ministry of agriculture and Food sciences Freetown Sierra Leone Beijing institute of Microbiology and Epidemiology Beijing China Ministry of Health and Sanitation Freetown Sierra Leone Beijing institute of Biotechnology Beijing China

Background Anthrax,a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis,remains a major global public health concern,especially in countries with limited resources.Sierra Leone,a West African country historically plagued by anthrax,has almost been out of report on this disease in recent decades.In this study,we described a large-scale anthrax outbreak affecting both animals and humans and attempted to characterize the path-ogenusingmoleculartechniques.Methods The causative agent of the animal outbreak in Port Loko District,Sierra Leone,between March and May 2022 was identified using the nanopore sequencing technique.A nationwide active surveillance was implemented from May 2022 to June 2023 to monitor the occurrence of anthrax-specific symptoms in humans.Suspected cases were subsequently verified using quantitative polymerase chain reaction.Full-genome sequencing was accomplished by combining long-read and short-read sequencing methods.Subsequent phylogenetic analysis was performed based on the full-chromosome single nucleotide polymorphisms.Results The outbreak in Port Loko District,Sierra Leone,led to the death of 233 animals between March 26th and May 16th,2022.We ruled out the initial suspicion of Anaplasma species and successfully identified B.anthracis as the causative agent of the outbreak.As a result of the government's prompt response,out of the 49 suspected human cases identifed during the one-year active surveillance,only 6 human cases tested positive,all within the frst month after the official declaration of the outbreak.The phylogenetic analysis indicated that the BaSL2022 isolate responsible for the outbreak was positioned in the A.Br.153 clade within the TransEuroAsian group of B.anthracis.Conclusions We successfully identifed a large-scale anthrax outbreak in Sierra Leone.The causative isolate of B.anthracis,BaSL2022,phylogenetically bridged other lineages in A.Br.153 clade and neighboring genetic groups,A.Br.144 and A.Br.148,eventually confirming the spillover of anthrax f

关键词： Molecular identification Anthrax Bacillus anthracis Sierra Leone Phylogeny Single nucleotide polymorphism

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Impacts of agri-food e-commerce on traditional wholesale industry:Evidence from China

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Journal of Integrative agriculture 2024年第4期23卷 1409-1428页

作者： Ruyi Yang Jifang Liu Shanshan Cao Wei Sun Fantao Kong institute of Agricultural Information Chinese Academy of Agricultural SciencesBeijing 100081China institute of Special Animal and Plant sciences Chinese Academy of Agricultural SciencesChangchun 130112China

Rapidly expanding studies investigate the effects of e-commerce on company operations in the retail market.However,the interaction between agri-food e-commerce(AEC)and the traditional agri-food wholesale industry(AWI)has not received enough attention in the existing literature.Based on the provincial panel data from 2013 to 2020 in China,this paper examines the effect of AEC on AWI,comprising three dimensions:digitalization(DIGITAL),agrifood e-commerce infrastructure and supporting services(AECI),and agri-food e-commerce economy(AECE).First,AWI and AEC are measured using an entropy-based combination of indicators.The results indicate that for China as a whole,AWI has remained practically unchanged,whereas AEC exhibits a significant rising trend.Second,the findings of the fixed-effect regression reveal that DIGITAL and AECE tend to raise AWI,whereas AECI negatively affects AWI.Third,threshold regression results indicate that AECI tends to diminish AWI with three-stage inhibitory intensity,which manifests as a first increase and then a drop in the inhibition degree.These results suggest that with the introduction of e-commerce for agricultural product circulation,digital development will have catfish effects that tend to stimulate the vitality of the conventional wholesale industry and promote technical progress.Furthermore,the traditional wholesale industry benefits financially from e-commerce even while it diverts part of the traditional wholesale circulation for agricultural products.

关键词： agri-food e-commerce traditional wholesale industry panel threshold model dual-channel circulation

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Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 254-270页

作者： Fulong NAN Wenlong NAN Xin YAN Hui WANG Shasha JIANG Shuyun ZHANG Zhongjie YU Xianjuan ZHANG Fengjun LIU Jun LI Xiaoqiong ZHOU Delei NIU Yiquan LI Wei WANG Ning SHI Ningyi JIN Changzhan XIE Xiaoni CUI He ZHANG Bin WANG Huijun LU Department of Special Medicine Department of Pathogenic BiologySchool of Basic MedicineQingdao UniversityQingdao 266071China China Animal Health and Epidemiology Center Qingdao 266032China Academician Workstation of Jilin Province Changchun University of Chinese MedicineChangchun 130117China institute of Virology Wenzhou UniversityWenzhou 325035China College of veterinary Medicine Jilin UniversityChangchun 130012China changchun veterinary research institute Chinese Academy of Agricultural SciencesChangchun 130122China Sino-Cell Biomed Co. Ltd.Qingdao 266000China

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen presentation.To elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-(IFN-),tumor necrosis factor-α(TNF-α),and IL-6 induced by DCs.Consequently,downregulated cytokines accelerated the infection and viral transmission from DCs to T cells.Furthermore,several other strains of NDV also exhibited inhibitory activity.The current study reveals that NDV can modulate the intensity of the innate-adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

关键词： Newcastle disease virus Dendritic cells Interleukin-12(IL-12) T cells Immunosuppression

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Effects of weaning on intestinal longitudinal muscle-myenteric plexus function in piglets

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Science China(Life sciences) 2024年第2期67卷 379-390页

作者： Jing Li Fenfen Liu Kaibin Mo Hengjia Ni Yulong Yin Key Laboratory of Agro-Ecological Processes in Subtropical Region Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessHunan Research Center of Livestock and Poultry SciencesSouth Central Experimental Station of Animal Nutrition and Feed Science in the Ministry of AgricultureInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China University of chinese academy of sciences Beijing 100008China Guangdong Key Laboratory for veterinary Drug Development and Safety Evaluation College of Veterinary MedicineSouth China Agricultural UniversityGuangzhou 510642China

Weaning piglets usually suffer from severe diarrhea(commonly known as postweaning diarrhea,PWD)along with intestinal motility disorder.Intestinal peristalsis is mainly regulated by the longitudinal muscle-myenteric plexus(LM-MP).To understand the relationship between intestinal LM-MP function and the development of PWD,we compared the intestinal electrical activity,and the transcriptional profile of the LM-MP between 21-day-old piglets(just weaned,n=7)and 24-day-old piglets(suffered the most severe weaning stress,n=7).The results showed that 24-day-old piglets exhibited different degrees of diarrhea.A significant increase in the slow-wave frequency in the ileum and colon was observed in 24-day-old piglets,while c-kit expression in the intestinal LM-MPs was significantly decreased,indicating that PWD caused by elevated slow-wave frequency may be associated with loss of c-kit.The real-time quantitative PCR(RT-q PCR)and enzyme-linked immunosorbent assay(ELISA)showed that intestinal LM-MPs in 24-day-old piglets may undergo inflammation and oxidative stress.Significant increases in 8-hydroxy-2′-deoxyguanosine and decreases in thioredoxin suggest that weaning may lead to DNA damage in the LM-MP of 24-day-old piglets.In addition,activating transcription factor 3 was significantly upregulated,indicating nerve damage in the LM-MP of 24-day-old piglets.The transcriptomic results showed that most of the differentially expressed genes in the ileal LM-MP after weaning were downregulated and closely related to the cell cycle process.Subsequent RT-q PCR analysis showed that the relative expression of p21 was upregulated,while the expression of cyclin A2,cyclin B1,and proliferating cell nuclear antigen was downregulated in the ileal and colonic LM-MP of 24-day-old piglets,suggesting that weaning may inhibit cell proliferation and cause G1/S cell cycle arrest in ileal and colonic LM-MP.In conclusion,weaning may lead to cell cycle arrest by causing DNA damage in the LM-MP,impairing intestinal motility regulation,and ultimately lea

关键词： weaning piglets diarrhea longitudinal muscle-myenteric plexus

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Control of highly pathogenic avian influenza through vaccination

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Journal of Integrative agriculture 2024年第5期23卷 1447-1453页

作者： Xianying Zeng Jianzhong Shi Hualan Chen State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin150069China

The stamping-out strategy has been used to control highly pathogenic avian influenza viruses in many countries,driven by the belief that vaccination would not be successful against such viruses and fears that avian influenza virus in vaccinated birds would evolve more rapidly and pose a greater risk to humans.In this review,we summarize the successes in controlling highly pathogenic avian influenza in China and make suggestions regarding the requirements for vaccine selection and effectiveness.In addition,we present evidence that vaccination of poultry not only eliminates human infection with avian influenza virus,but also significantly reduces and abolishes some harmful characteristics of avian influenza virus.

关键词： avian influenza control highly pathogenic vaccination

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Biology of Hippo signaling pathway:Skeletal muscle development and beyond

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Journal of Integrative agriculture 2024年第6期23卷 1825-1838页

作者： Shuqi Qin Chaocheng Li Haiyan Lu Yulong Feng Tao Guo Yusong Han Yongsheng Zhang Zhonglin Tang Xinjiang Characteristic Livestock Breeding and Reproduction Team College of Animal Science and TechnologyShihezi UniversityShihezi 832003China Lanzhou veterinary research institute Chinese Academy of Agricultural SciencesLanzhou 730046China Kunpeng institute of Modern agriculture at Foshan Foshan 528226China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518124China

Global demand for farm animals and their meat products i.e.,pork,chicken and other livestock meat,is steadily incresing.With the ongoing life science research and the rapid development of biotechnology,it is a great opportunity to develop advanced molecular breeding markers to efficiently improve animal meat production traits.Hippo is an important study subject because of its crucial role in the regulation of organ size.In recent years,with the increase of research on Hippo signaling pathway,the integrative application of multi-omics technologies such as genomics,transcriptomics,proteomics,and metabolomics can help promote the in-depth involvement of Hippo signaling pathway in skeletal muscle development research.The Hippo signaling pathway plays a key role in many biological events,including cell division,cell migration,cell proliferation,cell differentiation,cell apoptosis,as well as cell adhesion,cell polarity,homeostasis,maintenance of the face of mechanical overload,etc.Its influence on the development of skeletal muscle has important research value for enhancing the efficiency of animal husbandry production.In this study,we traced the origin of the Hippo pathway,comprehensively sorted out all the functional factors found in the pathway,deeply analyzed the molecular mechanism of its function,and classified it from a novel perspective based on its main functional domain and mode of action.Our aim is to systematically explore its regulatory role throughout skeletal muscle development.We specifically focus on the Hippo signaling pathway in embryonic stem cell development,muscle satellite cell fate determination,myogenesis,skeletal muscle meat production and organ size regulation,muscle hypertrophy and atrophy,muscle fiber formation and its transformation between different types,and cardiomyocytes.The roles in proliferation and regeneration are methodically summarized and analyzed comprehensively.The summary and prospect of the Hippo signaling pathway within this article will provide ideas for further improving

关键词： Hippo skeletal muscle organ size myogenesis C2C12 livestock animals

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Risk assessment of agricultural green water security in Northeast China under climate change

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Science China Earth sciences 2024年第7期67卷 2178-2194页

作者： Jingxuan SUN Guangxin ZHANG Yanfeng WU Liwen CHEN Peng QI Boting HU Yijun XU Northeast institute of Geography and Agroecology.chinese academy of sciences Changchun 130102China University of chinese academy of sciences Beijing 100049China State Key Laboratory of Black Soils Conservation and Utilization Northeast Institute of Geography and AgroecologyChinese Academy of SciencesChangchun 130102China School of Renewable Natural Resources Louisiana State University Agricultural Center227 Highland RoadBaton RougeLA 70803USA

Northeast China is an important base for grain production,dominated by rain-fed agriculture that relies on green water.However,in the context of global climate change,rising regional temperatures,changing precipitation patterns,and increasing drought frequency pose threats and challenges to agricultural green water security.This study provides a detailed assessment of the spatiotemporal characteristics and development trends of green water security risks in the Northeast region under the base period(2001-2020)and the future(2031-2090)climate change scenarios(SSP245 and SSP585)using the green water scarcity(GWS)index based on raster-scale crop spatial distribution data,Delta downscaling bias-corrected ERA5 data,and CMIP6 multimodal data.During the base period,the green water risk-free zone for dry crops is mainly distributed in the center and east of the Northeast region(72.4% of the total area),the low-risk zone is primarily located in the center(14.0%),and the medium-risk(8.3%)and high-risk(5.3%)zones are mostly in the west.Under SSP245 and SSP585 future climate change scenarios,the green water security risk shows an overall expansion from the west to the center and east,with the low-risk zone increasing to 21.6% and 23.8%,the medium-risk zone increasing to 16.0% and 17.9%,and the high-risk zone increasing to 6.9% and 6.8%,respectively.Considering dry crops with GWS greater than 0.1 as in need of irrigation,the irrigated area increases from 27.6%(base period)to 44.5%(SSP245)and 48.6%(SSP585),with corresponding increases in irrigation water requirement(IWR)of 4.64 and 5.92 billion m~3,respectively,which further exacerbates conflicts between supply and demand of agricultural water resources.In response to agricultural green water security risks,coping strategies such as evapotranspiration(ET)-based water resource management for dry crops and deficit irrigation are proposed.The results of this study can provide scientific basis and decision support for the development of Northeast irrigated agriculture and the cons

关键词： Climate change Food security Green water security risk Irrigation water requirement Green water scarcity

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Flavonoids from mulberry leaves inhibit fat production and improve fatty acid distribution in adipose tissue in finishing pigs

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Animal Nutrition 2024年第1期16卷 147-157页

作者： Yingying Liu Yinglin Peng Chen Chen Huibo Ren Ji Zhu Yuan Deng Qingming Cui Xionggui Hu Jianhua He Huali Li Xinghui Zhu Yulong Yin Jun He Yi Xiao College of Animal Science and Technology Hunan Agricultural University Hunan institute of Animal and veterinary Science Key Laboratory of Conservation and Genetic Analysis of Local Pig Breed Germplasm Resources College of Information and Intelligence Hunan Agricultural University institute of Subtropical agriculture Chinese Academy of Sciences

This study evaluated the effects of flavonoids from mulberry leaves (FML) on plasma biochemical indices,serum activities of lipid metabolism-related enzymes,fat morphology,fatty acid composition,and lipid metabolism in different adipose tissues of finishing pigs.We used 120 chinese hybrid barrows of Berkshire and Bama mini-pigs with an average initial body weight of 45.11±4.23 kg.The pigs were randomly assigned to five treatment groups and fed a control diet based on corn,soybean meal,and wheat bran or a control diet supplemented with 0.02%,0.04%,0.08%,or 0.16%FML.Each experimental group had six replicates (pens),with four pigs per pen.After a 7-d adaptation period,the feeding trial was conducted for 58 d.Blood and adipose tissue samples were collected from 30 pigs (one pig per pen)at the end of the test.The results showed that FML supplementation significantly decreased the feed intake to body gain ratio,the plasma concentrations of total cholesterol and free fatty acids,and the serum activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (linear or quadratic effects,P<0.05),and decreased the plasma triglyceride concentration (quadratic,P=0.07).Increasing FML supplementation increased the average daily gain and serum activities of lipoprotein lipase (linear and quadratic effects,P<0.05) and adipose triglyceride lipase (linear,P<0.05).Dietary FML supplementation decreased the adipocyte area in the dorsal subcutaneous adipose (DSA) tissue of finishing pigs (linear,P=0.05) and increased the adipocyte area in the visceral adipose tissue (quadratic,P<0.01).Increasing FML supplementation decreased the C20:1 content in DSA,abdominal subcutaneous adipose,and visceral adipose tissues of finishing pigs (P<0.05) and increased the C18:3n3 and n-3 PUFA contents(P<0.05).The lipid metabolism genes were regulated by the PPARγ-LXRa-ABCA1 signaling pathway,and their expressions differed in different adipose tissues.These findings suggest that FML improved growth performance,regulated lipid metabolism,inhibited fat production

关键词： Finishing pig Mulberry leaf Flavonoid Lipid metabolism Fatty acid Lard

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