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Precore mutation enhances viral replication to facilitate persistent infection especially in HBeAg-negative patients

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Virologica Sinica 2024年第2期39卷 319-330页

作者： Guixin Li Danli Yang Xin Liu Ting Zhang Hui Liu Jun Zou Zimeng Xu Xiangmei Chen Lizhong Dai Hongsong Chen Fengmin Lu Peking University People's Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijing International Cooperation Base for Science and Technology on NAFLD DiagnosisBeijing100044China Department of Microbiology and Infectious Disease Center School of Basic Medical SciencesPeking UniversityBeijing100191China Baruch S.Blumberg Institute DoylestownPA18901USA Shenzhen Sanyuansheng biotechnology Co. LtdShenzhen518000China Precision Medicine Center of Zhengzhou University Academy of Medical SciencesZhengzhou UniversityZhengzhou450001China Peking University-Sansure Biotech Joint laboratory of Molecular Medicine Sansure Biotech Co.LtdChangsha410205China

Naturally occurred precore(PC,G1896A)and/or basal core promoter(BCP,A1762T/G1764A)mutations are prevalent in chronic HBV-infected patients,especially those under HBeAg-negative ***,the replicative capacity of HBV with PC/BCP mutations remains ***,meta-analysis showed that,only under HBeAg-negative status,the serum HBV DNA load in patients with PC mutation was 7.41-fold higher than those without the *** PC mutation alone and BCPþPC mutations promoted HBV replication in cell and hydrodynamic injection mouse *** human hepatocyte chimeric mouse model,BCPþPC mutations led to elevated replicative capacity and intrahepatic core protein ***,preC RNA harboring PC mutation could serve as mRNA to express core and P proteins,and such pgRNA-like function favored the maintenance of cccDNA pool under HBeAg-negative ***,BCPþPC mutations induced more extensive and severe human hepatocyte damage as well as activated endoplasmic reticulum stress and TNF signaling pathway in livers of chimeric *** study indicates that HBeAg-negative patients should be monitored on HBV mutations regularly and are expected to receive early antiviral treatment to prevent disease progression.

关键词： Hepatitis B virus Precore mutation Basal core promoter mutations Endoplasmic reticulum stress

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Extracellular vesicles as tools and targets in therapy for diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 872-912页

作者： Mudasir A.Kumar Sadaf K.Baba Hana Q.Sadida Sara Al.Marzooqi Jayakumar Jerobin Faisal H.Altemani Naseh Algehainy Mohammad A.Alanazi Abdul-Badi Abou-Samra Rakesh Kumar Ammira S.Al-Shabeeb Akil Muzafar A.Macha Rashid Mir Ajaz A.Bhat Watson-Crick Centre for Molecular Medicine Islamic University of Science and TechnologyAwantiporaKashmir 192122India Department of Human Genetics-Precision Medicine in Diabetes Obesity and Cancer ProgramSidra MedicineDohaQatar Qatar Metabolic Institute Academic Health SystemHamad Medical CorporationDohaQatar Department of Medical laboratory Technology Prince Fahad Bin Sultan Chair for Biomedical ResearchFaculty of Applied Medical SciencesUniversity of TabukTabukSaudi Arabia School of biotechnology Shri Mata Vaishno Devi UniversityKatraIndia

Extracellular vesicles(EVs)are nano-sized,membranous structures secreted into the extracellular *** exhibit diverse sizes,contents,and surface markers and are ubiquitously released from cells under normal and pathological *** serum is a rich source of these EVs,though their isolation from serum proteins and non-EV lipid particles poses *** vesicles transport various cellular components such as proteins,mRNAs,miRNAs,DNA,and lipids across distances,influencing numerous physiological and pathological events,including those within the tumor microenvironment(TME).Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents,drug delivery systems,and disease *** in cancer diagnostics,EV detection can pave the way for early identification and offers potential as diagnostic ***,various EV subtypes are emerging as targeted drug delivery tools,highlighting their potential clinical *** need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains *** into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the *** this review,we discuss in detail the roles of EVs across various conditions,including cancers(encompassing head and neck,lung,gastric,breast,and hepatocellular carcinoma),neurodegenerative disorders,diabetes,viral infections,autoimmune and renal diseases,emphasizing the potential advancements in molecular diagnostics and drug delivery.

关键词： diseases sized sizes

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Zoonotic human liver flukes, a type 1 biocarcinogen, in freshwater fishes: genetic analysis and confirmation of molluscan vectors and reservoir hosts in Bangladesh

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贫困所致传染病(英文) 2024年第3期13卷 1-16页

作者： Labony Sharmin Shahid Alim Md. Abdul Hasan Muhammad Mehedi Hossain Md. Shahadat Akter Sharmin Paul Joydeep Farjana Thahsin Ali Md. Haydar Alam Mohammad Zahangir Hatta Takeshi Kawada Hayato Mizutani Keiko Tsuji Naotoshi Anisuzzaman Department of Parasitology Faculty of Veterinary Science Bangladesh Agricultural University Mymensingh Bangladesh Department of Fisheries Technology Faculty of Fisheries Bangladesh Agricultural University Mymensingh Bangladesh Department of biotechnology School of Life Sciences &amp biotechnology Adamas University Barasat - Barrackpore Rd Jagannathpur Kolkata West Bengal India Department of Pathology and Parasitology Hajee Mohammad Danesh Science and Technology University Dinajpur Bangladesh Department of Parasitology and Tropical Medicine Kitasato University School of Medicine-15-Kitasato Minami Sagamihara Kanagawa-0374 Japan Department of Molecular and Cellular Parasitology Kitasato University Graduate School of Medical Sciences-15-Kitasato Minami Sagamihara Kanagawa-0373 Japan

Background Opisthorchiid flukes, particularlyOpisthorchis viverrini,Opisthorchis felineus,Clonorchis sinensis, andMetorchis spp. are the most common fish-borne zoonotic human liver flukes (hLFs). Liver fluke infections are more prevalent in resource-deprived and underprivileged areas. We herein estimated the prevalence of the metacercariae (MC) of major hLFs in common large freshwater fishes (lFWF) marketed for human consumption from some selected areas of Bangladesh along with detection of their molluscan vectors and *** The current status of fish-borne zoonotic hLF infections in lFWF was investigated along with their molluscan vectors and mammalian reservoir hosts in Mymensingh and Kishoreganj in Bangladesh from July 2018–June 2022 using conventional and multiple molecular techniques, such as PCR, PCR-restriction fragment length polymorphism (RFLP), sequencing, and bioinformatic analyses. The infection rate of fishes was analyzed using theZ-test and the loads of MC were compared using the chi-squared (χ2) *** The MC ofC. sinensis,Opisthorchis spp., andMetorchis spp. were detected in 11 species of common and popular lFWF. In lFWF, the estimated prevalence was 18.7% and the mean load was 137.4 ± 149.8 MC per 100 g of fish. The prevalence was the highest (P 0.05) distributed between the head and body of fishes. The infection rate was slightly higher in cultured (19.6%) fishes. The MC ofC. sinensis,O. felineus,O. viverrini, andMetorchis orientalis in fishes were confirmed using PCR, PCR-RFLP and bioinformatics. The cercariae of opisthorchiid (Pleurolophocercus cercariae) flukes were only recovered fromBithynia spp. (3.9%, 42 out of 1089). The ova of hLFs from dogs (4.3%, 5 out of 116) and cats (6.0%, 6 out of 100), and adult flukes (***) from ducks

关键词： Human liver fluke Freshwater fish Molluscan vector Reservoir host Bangladesh

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AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken

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Science China(Life Sciences) 2024年第7期67卷 1468-1478页

作者： Jiang Deng Jia-Cheng Yang Yue Feng Ze-Jing Xu Kamil Kuča Meng Liu Lv-Hui Sun State Key laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhan 430070China Department of Chemistry Faculty of ScienceUniversity of Hradec KraloveHradec Kralove 50003Czech Republic

Dietary exposure to aflatoxin B1(AFB1)is harmful to the health and performance of domestic *** hepatic cytochrome P450s(CYPs),CYP1A1 and CYP2A6,are the primary enzymes responsible for the bioactivation of AFB1to the highly toxic exo-AFB1-8,9-epoxide(AFBO)in ***,the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1metabolism remains ***-luciferase reporter assay,bioinformatics and site-directed mutation results indicated that specificity protein 1(SP1)and activator protein-1(AP-1)motifs were located in the core region-1,063/-948,-606/-541 of the CYP1A1 promoter as well as-636/-595,-503/-462,-147/-1 of the CYP2A6 ***,overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and ***,bioactivation of AFB1to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression,which was trans-activated owing to the upregulation of AP-1,rather than SP1,stimulated by AFB1-induced reactive oxygen ***,nano-selenium could reduce ROS,downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6,thus alleviating the toxicity of *** conclusion,AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1to AFBO in chicken liver,which could provide novel targets for the remediation of aflatoxicosis in chicks.

关键词： aflatoxin B1 CYP1A1 CYP2A6 SP1 AP-1 transcriptional activation

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OsPRMT6a-mediated arginine methylation of OsJAZ1 regulates jasmonate signaling and spikelet development in rice

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Molecular Plant 2024年第6期17卷 900-919页

作者： Kun Dong Fuqing Wu Siqi Cheng Shuai Li Feng Zhang Xinxin Xing Xin Jin Sheng Luo Miao Feng Rong Miao Yanqi Chang Shuang Zhang Xiaoman You Peiran Wang Xin Zhang Cailin Lei Yulong Ren Shanshan Zhu Xiuping Guo Chuanyin Wu Dong-Lei Yang Qibing Lin Zhijun Cheng Jianmin Wan State Key laboratory of Crop Gene Resources and Breeding National Key Facility for Crop Gene Resources and Genetic ImprovementInstitute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China State Key laboratory for Crop Genetics and Germplasm Enhancement Nanjing Agricultural UniversityNanjing 210095China

Although both protein arginine methylation(PRMT)and jasmonate(JA)signaling are crucial for regulating plant development,the relationship between these processes in the control of spikelet development remains *** this study,we used the CRISPR/Cas9 technology to generate two OsPRMT6a loss-of-function mutants that exhibit various abnormal spikelet ***,we found that OsPRMT6a can methylate arginine residues in JA signal repressors OsJAZ1 and *** showed that arginine methylation of OsJAZ1 enhances the binding affinity of OsJAZ1 with the JA receptors OsCOI1a and OsCOI1b in the presence of JAs,thereby promoting the ubiquitination of OsJAZ1 by the SCF^(OsCOI1a/OsCOI1b) complex and degradation via the 26S *** process ultimately releases OsMYC2,a core transcriptional regulator in the JA signaling pathway,to activate or repress JA-responsive genes,thereby maintaining normal plant(spikelet)***,in the osprmt6a-1 mutant,reduced arginine methylation of OsJAZ1 impaires the interaction between OsJAZ1 and OsCOI1a/OsCOI1b in the presence of *** a result,OsJAZ1 proteins become more stable,repressing JA responses,thus causing the formation of abnormal spikelet ***,we discovered that JA signaling reduces the OsPRMT6a mRNA level in an OsMYC2-dependent manner,thereby establishing a negative feedback loop to balance JA *** further found that OsPRMT6a-mediated arginine methylation of OsJAZ1 likely serves as a switch to tune JA signaling to maintain normal spikelet development under harsh environmental conditions such as high ***,our study establishes a direct molecular link between arginine methylation and JA signaling in rice.

关键词： protein arginine methylation jasmonate signaling negative feedback loop spikelet development adaptation to heat stress rice

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Large‑scale transcriptomic and genomic analyses reveal a novel functional gene SERPINB6 for chicken carcass traits

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Journal of Animal Science and biotechnology 2024年第4期15卷 1466-1481页

作者： Di Zhao Ranran Liu Xiaodong Tan Huimin Kang Jie Wang Zheng Ma Haiquan Zhao Hai Xiang Zhengfen Zhang Hua Li Guiping Zhao Guangdong Provincial Key laboratory of Animal Molecular Design and Precise Breeding School of Life Science and EngineeringFoshan UniversityFoshanChina State Key laboratory of Animal Biotech Breeding Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijingChina Guangdong Tinoo’s Foods Group Co. Ltd.QingyuanChina

Background Carcass traits are crucial indicators of meat production ***,the molecular regulatory mechanisms associated with these traits remain *** In this study,we conducted comprehensive transcriptomic and genomic analyses on 399 Tiannong partridge chickens to identify key genes and variants associated with carcass traits and to elucidate the underlying regulatory *** on association analyses with the elastic net(EN)model,we identified 12 candidate genes(AMY1A,AP3B2,CEBPG,EEF2,EIF4EBP1,FGFR1,FOXD3,GOLM1,LOC107052698,PABPC1,SERPINB6 and TBC1D16)for 4 carcass-related traits,namely live weight,dressed weight,eviscerated weight,and breast muscle ***6 was identified as the only overlapping gene by 3 analyses,EN model analysis,weighted gene co-expression network analysis and differential expression ***-level experiments confirmed that SERPINB6 promotes the proliferation of chicken DF1 cells and primary *** expression genome-wide association study and association analysis indicated that rs317934171 is the critical site that enhances SERPINB6 ***,a dual-luciferase reporter assay proved that gga-miR-1615 targets the 3′UTR of *** Collectively,our findings reveal that SERPINB6 serves as a novel gene for chicken carcass traits by promoting fibroblast and myoblast ***,the downstream variant rs317934171 regulates SERPINB6 *** results identify a new target gene and molecular marker for the molecular mechanisms of chicken carcass traits.

关键词： Carcass traits Chicken Genome SERPINB6 Transcriptome

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Insights into genetic diversity and phenotypic variations in domestic geese through comprehensive population and pan-genome analysis

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Journal of Animal Science and biotechnology 2024年第1期15卷 88-107页

作者： Guangliang Gao Hongmei Zhang Jiangping Ni Xianzhi Zhao Keshan Zhang Jian Wang Xiangdong Kong Qigui Wang Chongqing Academy of Animal Science Rongchang DistrictChongqing 402460China Livestock and Poultry Multi‑Omics Key laboratory of Ministry of Agriculture and Rural Affairs College of Animal Science and TechnologySichuan Agricultural UniversityChengdu 611130China Chongqing Engineering Research Center of Goose Genetic Improvement Rongchang DistrictChongqing 402460China Department of Cardiovascular Ultrasound and Non‑Invasive Cardiology Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu611731China Ultrasound in Cardiac Electrophysiology and Biomechanics Key laboratory of Sichuan Province University of Electronic Science and Technology of ChinaChengdu611731China JiguangGene biotechnology Co. Ltd.Nanjing210032China Jiangsu Agri-Animal Vocational College Taizhou225300China Poultry Science Institute Chongqing Academy of Animal ScienceNo.51 Changzhou AvenueRongchang DistrictChongqing 402460P.R.China

Background Domestic goose breeds are descended from either the Swan goose(Anser cygnoides)or the Greylag goose(Anser anser),exhibiting variations in body size,reproductive performance,egg production,feather color,and other phenotypic *** a pan-genome facilitates a thorough identification of genetic variations,thereby deepening our comprehension of the molecular mechanisms underlying genetic diversity and phenotypic *** To comprehensively facilitate population genomic and pan-genomic analyses in geese,we embarked on the task of 659 geese whole genome resequencing data and compiling a database of 155 RNA-seq *** constructing the pan-genome for geese,we generated non-reference contigs totaling 612 Mb,unveiling a collection of 2,813 novel genes and pinpointing 15,567 core genes,1,324 softcore genes,2,734 shell genes,and 878 cloud genes in goose ***,we detected an 81.97 Mb genomic region showing signs of genome selection,encompassing the TGFBR2 gene correlated with variations in body weight among ***-wide association studies utilizing single nucleotide polymorphisms(SNPs)and presence-absence variation revealed significant genomic associations with various goose meat quality,reproductive,and body composition *** instance,a gene encoding the SVEP1 protein was linked to carcass oblique length,and a distinct gene-CDS haplotype of the SVEP1 gene exhibited an association with carcass oblique ***,the pan-genome analysis revealed enrichment of variable genes in the“hair follicle maturation”Gene Ontology term,potentially linked to the selection of feather-related traits in geese.A gene presence-absence variation analysis suggested a reduced frequency of genes associated with“regulation of heart contraction”in domesticated geese compared to their wild *** study provided novel insights into gene expression features and functions by integrating gene expression patterns across multiple orga

关键词： Gene-CDS haplotype Goose GWAS Pan-genome Presence-absence variation Selection signal

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Copper naphthalocyanine-based hole-transport material for highperformance and thermally stable perovskite solar cells

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Science China Chemistry 2024年第8期67卷 2701-2709页

作者： Yue Qiang Huaiman Cao Yuzhen Pan Yi Chi Liangyu Zhao Yingguo Yang Hai-Bei Li Yan Gao Licheng Sun Ze Yu State Key laboratory of Fine Chemicals Frontier Science Center for Smart MaterialsDalian University of Technology(DUT).Dalian 116024China School of Chemistry Dalian University of Technology(DUT)Dalian 116024China School of Microelectronics Fudan UniversityShanghai 200433China Shanghai Synchrotron Radiation Facility(SSRF) Zhangjiang LabShanghai Advanced Research InstituteShanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai 201800China School of Ocean Shandong UniversityWeihai 264209China Center of Artificial Photosynthesis for Solar Fuels and Department of Chemistry School of ScienceWestlake UniversityHangzhou 310024China Department of Chemistry School of Engineering Sciences in ChemistryBiotechnology and HealthKTH Royal Institute of Technology Stockholm 10044Sweden

Metal phthalocyanines(MPcs) have gained considerable research attention as hole-transport materials(HTMs) in perovskite solar cells(PSCs) because of their superb stability. However, the photovoltaic performance of MPc-based HTMs in PSCs is still lagging behind their small molecule and polymeric counterparts, largely due to their relatively low hole mobility. Here, we report for the first time the application of a copper naphthalocyanine derivative(namely t Bu-Cu Nc) as a hole-transport material(HTM)in perovskite solar cells(PSCs), and systematically study its optoelectronic and photovoltaic property compared with its Cu Pc analog(t Bu-Cu Pc). Combined experiments disclose that the extension of π-conjugation from Pc to Nc core leads to not only an enhanced hole-carrier mobility associated with a stronger intermolecular interaction, but also an elevated glass transition temperature(T_g) of 252 °C. The resultant PSCs employing t Bu-Cu Nc deliver an excellent power conversion efficiency of 24.03%, which is the record efficiency reported for metal complex-based HTMs in PSCs. More importantly, the encapsulated t Bu-Cu Nc-based devices also show dramatically improved thermal stability than the devices using the well-known SpiroOMe TAD, with a T_(80)lifetime for more than 1,000 h under damp-heat stress. This study unfolds a new avenue for developing efficient and stable HTMs in PSCs.

关键词： hole-transport materials perovskite solar cells copper naphthalocyanine extendedπ-conjugation thermal stability

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Adiponectin restores the obesity-induced impaired immunomodulatory function of mesenchymal stromal cells via glycolytic reprogramming

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Acta Pharmaceutica Sinica B 2024年第1期14卷 273-291页

作者： Duc-Vinh Pham Thi-Kem Nguyen Bao-Loc Nguyen Jong-Oh Kim Jee-Heon Jeong Inho Choi Pil-Hoon Park Department of Pharmacology Hanoi University of PharmacyHanoi 100000Viet Nam College of Pharmacy Yeungnam UniversityGyeongsan 38541Republic of Korea Department of Medical biotechnology Yeungnam UniversityGyeongsan 38541Republic of Korea Research Institute of Cell Culture Yeungnam UniversityGyeongsan 38541Republic of Korea Department of Precision Medicine School of MedicineSungkyunkwan UniversitySuwon 16419Republic of Korea

Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells(MSC).However,it remains unclear what drives the compromised potency of obese *** this study,we examined the involvement of adiponectin,an adipose tissuederived hormone,in obesity-induced impaired therapeutic function of ***-induced obesity leads to a decrease in serum adiponectin,accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC(ADSC).Interestingly,priming with globular adiponectin(gAcrp)improved the immunomodulatory potential of obese *** effects were also observed in lean *** addition,gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced ***,while obesity inhibited the glycolytic capacity of MSC,gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1a *** findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

关键词： Adiponectin Adipose-derived stromal cells Colitis Glycolytic induction HIF1a Immunomodulation Mesenchymal stromal cells Obesity

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AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFBin chicken

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Science China Life Sciences 2024年

作者： Jiang Deng Jia-Cheng Yang Yue Feng Ze-Jing Xu Kamil Ku?a Meng Liu Lv-Hui Sun State Key laboratory of Agricultural Microbiology Hubei Hongshan Laboratory Frontiers Science Center for Animal Breeding and Sustainable Production College of Animal Sciences and TechnologyHuazhong Agricultural University Department of Chemistry Faculty of Science University of Hradec Kralove

Dietary exposure to aflatoxin B1(AFB1) is harmful to the health and performance of domestic *** hepatic cytochrome P450s(CYPs),CYP1A1 and CYP2A6,are the primary enzymes responsible for the bioactivation of AFB1to the highly toxic exo-AFB1-8,9-epoxide(AFBO) in ***,the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1metabolism remains ***-luciferase reporter assay,bioinformatics and site-directed mutation results indicated that specificity protein 1 (SP1) and activator protein-1 (AP-1) motifs were located in the core region-1,063/-948,-606/-541 of the CYP1A1 promoter as well as-636/-595,-503/-462,-147/-1 of the CYP2A6 ***,overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and ***,bioactivation of AFB1to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression,which was trans-activated owing to the upregulation of AP-1,rather than SP1,stimulated by AFB1-induced reactive oxygen ***,nano-selenium could reduce ROS,downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6,thus alleviating the toxicity of *** conclusion,AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1to AFBO in chicken liver,which could provide novel targets for the remediation of aflatoxicosis in chicks.

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