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Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms

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Asian Journal of Pharmaceutical sciences 2024年第3期19卷 164-180页

作者： Xilong Cui Fanhui Liu Shuang Cai Tingting Wang Sidi Zheng Xinshu Zou Linlin Wang Siqi He Yanhua Li Zhiyun Zhang college of Veterinary Medicine Northeast Agricultural University Heilongjiang Key Laboratory for animal Disease Control and Pharmaceutical Development

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm ***-based nanoplatform is a promising emerging approach for treatment of biofilm ***,their therapeutic efficacy was restricted by the low drug loading capacity and lack of ***,we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm.A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized,and then encapsulated into the amphiphilic quaternized *** obtained ISL-G2loaded NPs possessed positively charged surface,which allowed cis-aconityl-D-tyrosine(CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr *** NPs maintained their negatively charged surface,thus prolonging the blood circulation *** response to low pH in the biofilms,the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive,which enhanced the accumulation and penetration of NPs in the ***,the pH-triggered release of D-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm *** in vivo study was performed on a MRSA biofilm infected wound *** phytochemical-based system led to～2log CFU (>99%) reduction of biofilm MRSA as compared to untreated wound (P<0.001)with negligible biotoxicity in *** phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

关键词： MRSA biofilm Isoliquiritigenin Dimer prodrug Charge adaptive Responsive nanoparticles

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Large-Scale CRISPR Screen of LDLR Pathogenic Variants

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Research 2024年第2期2023卷 213-225页

作者： Mengjing Li Lerong Ma Yiwu Chen Jianing Li Yanbing Wang Wenni You Hongming Yuan Xiaochun Tang Hongsheng Ouyang Daxin Pang Key Lab for Zoonoses Research Ministry of EducationAnimal Genome Editing Technology Innovation CenterCollege of Animal SciencesJilin UniversityChangchunJilin Province 130062China The Institute of Translational Medicine Tianjin Union Medical Center of Nankai UniversityTianjin 300071China Chongqing ResearchInstitute Jilin UniversityChongqing 401123China Chongqing Jitang Biotechnology Research Institute Co.Ltd. ChongqingChina

Familial hypercholesterolemia(FH)is a frequently occurring genetic disorder that is linked to early-onset cardiovascular *** left untreated,patients with this condition can develop severe cardiovascular ***,many patients remain undiagnosed,and even when diagnosed,the treatment is often not *** mutations in the LDLR gene are the primary cause of FH,predicting whether novel variants are pathogenic is not a straightforward *** the functionality of LDLR variants is crucial in uncovering the genetic basis of *** study utilized CRISPR/Cas9 cytosine base editors in pooled screens to establish a novel approach for functionally assessing tens of thousands of LDLR variants on a large scale.A total of more than 100 single guide RNAs(sgRNAs)targeting LDLR pathogenic mutations were successfully screened with relatively high *** of these,5 sgRNAs were further subjected to functional verification studies,including 1 in the promoter,1 in the antisense RNA,1 in the exon,and 2 in the *** for the variant caused by the sgRNA located at intron 16,the functionalities of the other LDLR variants were all *** high similarity of LDLR intron sequences may lead to some false ***,these results confirm the reliability of the large-scale screening strategy for functional analysis of LDLR variants,and the screened candidate pathogenic mutations could be used as an auxiliary means of clinical gene detection to prevent FH-induced heart disease.

关键词： LDLR Screen straight

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Ancient mitochondrial genome depicts sheep maternal dispersal and migration in Eastern Asia

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Journal of Genetics and Genomics 2024年第1期51卷 87-95页

作者： Liu Yang Xing Zhang Yaning Hu Piao Zhu Hua Li Zhenyu Peng Hai Xiang Xinying Zhou Xingbo Zhao National Engineering Laboratory for animal Breeding Key Laboratory of AnimalGeneticsBreeding and ReproductionMinistry of Agriculture and Rural AffairsCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Guangdong Provincial Key Laboratory of animal Molecular Design and Precise Breeding School of Life Science and EngineeringFoshan UniversityFoshanGuangdong 528225China State Key Laboratory of Agricultural Genomics BGI-ShenzhenShenzhenGuangdong 518083China Key Laboratory of Vertebrate Evolution and Human Origins Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China

Sheep have been one of the most important groups of animals since ancient ***,the knowledge of their migration routes and genetic relationships is still poorly *** investigate sheep maternal migration histories alongside Eurasian communications routes,in this study,we obtain mitochondrial genomes(mitogenomes)from 17 sheep remains in 6 Chinese sites and 1 Uzbekistan site dated 4429–3100 years before present(BP).By obtaining the mitogenomes from the sheep(4429–3556 BP)found in the Tongtian Cave site in Xinjiang,Altai region of northwest China,our results support the emergence of haplogroup C sheep in Xinjiang as early as 4429–3556 *** combined phylogenetic analyses with extant ancient and modern sheep mitogenomes suggest that the Uzbekistan-Altai region may have been a migration hub for early sheep in eastern *** least two migration events have taken place for sheep crossing Eurasia to China,one passing by Uzbekistan and Northwest China to the middle and lower reaches of the Yellow River at approximately 4000 BP and another following the Altai region to middle Inner Mongolia from 4429 BP to 2500 ***,this study provides further evidence for early sheep utilization and migration patterns in Eastern Asia.

关键词： Sheep Ancient DNA Eastern Asia Mitochondrial genome Migration Altai

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Blastoids generated purely from embryonic stem cells both in mice and humans

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Science China(Life sciences) 2024年第2期67卷 418-420页

作者： Baojiang Wu Yanqiu Wang Jia Yan Mengya Liu Xihe Li Fuchou Tang Siqin Bao The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock Inner Mongolia UniversityHohhot 010020China Research Center for animal Genetic Resources of Mongolia Plateau College of Life SciencesInner Mongolia UniversityHohhot 010020China Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center College of Life SciencesPeking UniversityBeijing 100871China Inner Mongolia Saikexing Institute of Breeding and Reproductive Biotechnology in Domestic animal Hohhot 011517China

Dear Editor,Embryonic stem cells(ESCs)and trophoblast stem cells(TSCs)are derived from blastocysts(Lu et al.,2001).Blastocyst-like structures(blastoids)are self-assembled structures formed by a combination of ESCs and TSCs(Rivron et al.,2018).To increase the success rate of blastoid formation and its similarity with the features of blastocysts,some reports showed that blastoid could also be derived from a combination of three cell lines,ESCs,TSCs,and extraembryonic endoderm cells(XENs),or novel type of stem cells(Sozen et al.,2018;Weatherbee et al.,2023:Wu et al.,2023;Zhang et al.,2023;Zhang et al.,2019).

关键词： purely similarity

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The evolution,pathogenicity and transmissibility of quadruple reassortant H1N2 swine influenza virus in China:A potential threat to public health

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Virologica Sinica 2024年第2期39卷 205-217页

作者： Xinxin Cui Jinhuan Ma Zifeng Pang Lingzhi Chi Cuishan Mai Hanlin Liu Ming Liao Hailiang Sun college of Veterinary Medicine South China Agricultural UniversityGuangzhou510642China Key Laboratory of Zoonosis Control and Prevention of Guangdong Province South China Agricultural UniversityGuangzhou510642China National and Regional Joint Engineering Laboratory for Medicament of Zoonosis Prevention and Control South China Agricultural UniversityGuangzhou510642China Shandong Vocational animal Science and Veterinary college Weifang261061China Institute of animal Health Guangdong Academy of Agricultural SciencesGuangzhou510640China

Swine are regarded as“intermediate hosts”or“mixing vessels”of influenza viruses,capable of generating strains with pandemic *** 2020 to 2021,we conducted surveillance on swine H1N2 influenza(swH1N2)viruses in swine farms located in Guangdong,Yunnan,and Guizhou provinces in southern China,as well as Henan and Shandong provinces in northern *** systematically analyzed the evolution and pathogenicity of swH1N2 isolates,and characterized their replication and transmission *** isolated viruses are quadruple reassortant H1N2 viruses containing genes from pdm/09 H1N1(PB2,PB1,PA and NP genes),triple-reassortant swine(NS gene),Eurasian Avian-like(HA and M genes),and recent human H3N2(NA gene)*** NA,PB2,and NP of SW/188/20 and SW/198/20 show high gene similarities to A/Guangdong/Yue Fang277/2017(H3N2).The HA gene of swH1N2 exhibits a high evolutionary *** five swH1N2 isolates replicate efficiently in human,canine,and swine cells,as well as in the turbinate,trachea,and lungs of mice.A/swine/Shandong/198/2020 strain efficiently replicates in the respiratory tract of pigs and effectively transmitted among ***,these current swH1N2 viruses possess zoonotic potential,highlighting the need for strengthened surveillance of swH1N2 viruses.

关键词： Swine influenza virus(SIV) H1N2 Evolution Replication Pathogenicity Zoonotic potential

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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 *** 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 *** 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 *** 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 *** addition,activating transcription factor 3 was significantly upregulated,indicating nerve damage in the LM-MP of 24-day-old *** 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 *** 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 *** conclusion,weaning may lead to cell cycle arrest by causing DNA damage in the LM-MP,impairing i

关键词： weaning piglets diarrhea longitudinal muscle-myenteric plexus

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Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs

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Journal of animal Science and Biotechnology 2024年第1期15卷 108-126页

作者： Tianqi Duo Xiaohong Liu Delin Mo Yu Bian Shufang Cai Min Wang Ruiqiang Li Qi Zhu Xian Tong Ziyun Liang Weilun Jiang Shiyi Chen Yaosheng Chen Zuyong He State Key Laboratory of Biocontrol School of Life SciencesSun Yat-Sen UniversityGuangzhou 510275GuangdongChina Department of Pharmacology(the State‑Province Key Laboratories of Biomedicine‑Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Hunan Provincial Key Laboratory for Genetic Improvement of Domestic animal College of Animal Science and TechnologyHunan Agricultural UniversityChangsha 410128China

Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat ***-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat *** favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig *** improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) *** We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote *** We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling *** study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing.

关键词： CBE3 IGF2 Intramuscular fat Meat production PI3K-AKT/AMPK ZBED6

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Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection

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Zoological Research 2024年第4期45卷 833-844页

作者： Ying Liu Lin Yang Hong-Yong Xiang Ming Niu Jia-Cheng Deng Xue-Yuan Li Wen-Jie Hao Hong-Sheng Ou-Yang Tong-Yu Liu Xiao-Chun Tang Da-Xin Pang Hong-Ming Yuan State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Animal Genome Editing Technology Innovation CenterCollege of Animal SciencesJilin UniversityChangchunJilin 130062China Chifeng Best Genetics Technology Co. Ltd.ChifengNei Mongol 024000China Chongqing Jitang Biotechnology Research Institute Co. Ltd.Chongqing 400015China

Porcine reproductive and respiratory syndrome(PRRS)is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus(PRRSV),resulting in substantial economic losses in the swine *** the CD163 SRCR5 domain,either through deletion or substitution,can eff1ectively confer resistance to PRRSV infection in ***,large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth *** the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant *** the current study,we identified a specific functional amino acid in CD163 that influences PRRSV *** infection experiments conducted on Marc145 and PK-15CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV(HP-PRRSV)proliferation by preventing viral binding and ***,individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type(WT)pigs,confirming effective resistance to *** of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G *** findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs,providing novel insights into controlling future PRRSV outbreaks.

关键词： PRRSV CD163 Point mutation E529G Pigs

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Transcriptome-based analysis of key signaling pathways affecting the formation of primordial germ cell in chickens

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Journal of Integrative Agriculture 2024年第5期23卷 1644-1657页

作者： Ying Ding Qiong Zhi Qisheng Zuo Kai Jin Wei Han Bichun Li Key Laboratory of animal Genetics Breeding and Molecular Design of Jiangsu ProvinceCollege of Animal Science and TechnologyYangzhou UniversityYangzhou 225009China Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China Yangzhou UniversityYangzhou225009China Poultry Research Institute Chinese Academy of Agricultural Sciences/Jiangsu Institute of Poultry ScienceYangzhou 225009China

Bone morphogenetic protein 4(BMP4)can induce the formation of chicken primordial germ cells(PGCs)in vitro;however,its regulatory mechanism in poultry remains *** study aimed to use RNA-seq to analyze PGCs in chicken embryos and iPGCs induced by BMP4 in vitro,clarify the internal regulatory factors of PGCs,analyze the mechanism of the formation of PGCs,and lay a theoretical foundation for the further optimization of PGCs induction *** stem cells(ESCs),PGCs and iPGCs induced by BMP4 in vitro were *** transcriptional maps of the three cell types were studied using *** results showed 6,142 genes differentially expressed between PGCs and iPGCs,of which 2,728 were upregulated in iPGCs and 3,414 were downregulated in *** to that in ESCs,BMP4 was significantly upregulated in PGCs and *** results showed that both the TGF-βand Wnt signaling pathways were activated during the formation of PGCs in vitro and in vivo,and the activation was more significant during iPGCs induced by *** expression of Nodal,an inhibitory factor of TGF-βsignaling,was significantly decreased in PGCs and iPGCs,but was not expressed in iPGCs,which further supports our ***,the Lysosome and PI3K-AKT signaling pathways were significantly enriched in PGCs and iPGCs,***,transmission electron microscopy(TEM)results showed that the number of autolysosomes was significantly higher after the addition of BMP4,which is consistent with the KEGG ***,the number of PGCs was significantly reduced after ATG14 was interfered in vivo and in *** conclusion,this study screened out the key signaling pathways during the formation of PGCs,aiming to provide help for enriching the mechanism network regulating PGCs formation in chicken and laying a theoretical foundation for further improving the efficiency of inducing PGCs in vitro.

关键词： RNA-seq BMP4 PGCs ATG14 chicken

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Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

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Zoological Research 2024年第1期45卷 79-94页

作者： Ya-Ling Zhu Lei-Lei Meng Jin-Hu Ma Xin Yuan Shu-Wen Chen Xin-Rui Yi Xin-Yu Li Yi Wang Yun-Shu Tang Min Xue Mei-Zi Zhu Jin Peng Xue-Jin Lu Jian-Zhen Huang Zi-Chen Song Chong Wu Ke-Zhong Zheng Qing-Qing Dai Fan Huang Hao-Shu Fang Department of Pathophysiology Anhui Medical UniversityHefeiAnhui 230032China Laboratory animal Research Center School of Basic Medical SciencesAnhui Medical UniversityHefeiAnhui 230032China Department of Hepatobiliary Surgery First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China college of animal Science and Technology Jiangxi Agricultural UniversityNanchangJiangxi 330045China

Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain ***,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP ***,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory *** total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD *** on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating *** study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.

关键词： Non-alcoholic fatty liver disease C/EBPβ Lipopolysaccharide-binding protein H3K27ac Integrative analysis Enhancer

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