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Genome-wide CRISPR screens identify CLC-2 as a drug target for anti-herpesvirus therapy:tackling herpesvirus drug resistance

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Science China(Life sciences) 2025年第2期68卷 515-526页

作者： Fayu Yang Nan Wei Shuo Cai Jing Liu Qingping Lan Hao Zhang Lu Shang Bo Zheng Mi Wang Yingchun Liu Lifang Zhang Chenzhong Fei Wu Tong Changlong Liu Ersheng Kuang Guangzhi Tong Feng Gu Shanghai veterinary Research Institute Chinese Academy of Agricultural SciencesShanghai 200241China Key Laboratory of veterinary Chemical Drugs and Pharmaceutics Ministry of Agriculture and Rural AffairsShanghai 200241China State Key Laboratory for Animal Disease Control and Prevention College of Veterinary MedicineLanzhou UniversityLanzhou Veterinary Research InstituteChinese Academy of Agricultural SciencesLanzhou 730000China Institute of Human Virology Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhou 510080China School of Medicine Tsinghua UniversityBeijing 100084China

The emergence of drug resistance to virus(i.e.,acyclovir(ACV)to herpesviruses)has been termed one of the common clinical issues,emphasizing the discovery of new antiviral *** address it,a genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)screening was performed in mouse haploid embryonic stem cells infected with pseudorabies virus(PRV),anα-herpesvirus causing human and pig *** results demonstrated that type 2 voltage-gated chloride channels(CLC-2)encoded by one of the identified genes,CLCN2,is a potential drug target for anti-herpesvirus ***-2 inhibitors,omeprazole(OME)and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid(DIDS),can efficiently inhibit infection of multiple herpesviruses in cellulo(i.e.,PRV,HSV and EBV),and effectively treat murine herpes simplex encephalitis(HSE).Additionally,DIDS was found to inhibit HSV-1 replication by blocking the PI3K/Akt *** importantly,both DIDS and OME were able to inhibit ACV-resistant HSV-1 strain *** study's findings suggest that targeting host-cell factors such as CLC-2 may be a promising approach to tackling herpesvirus drug *** discovery of CLC-2 as a potential drug target for anti-herpesvirus therapy provides a new direction for the development of novel antiviral agents.

关键词： herpesviruses CRISPR host-directed therapy CLC-2 DIDS

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The assembly and activation of the PANoptosome promote porcine granulosa cell programmed cell death during follicular atresia

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Journal of Animal Science and Biotechnology 2025年第1期16卷 121-135页

作者： Hao Wu Yingxue Han Jikang Liu Rong Zhao Shizhen Dai Yajun Guo Nan Li Feng Yang Shenming Zeng National Engineering Laboratory for Animal Breeding Key Laboratory of Animal Genetics and Breeding of the Ministry of AgricultureCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Department of Clinical sciences College of Veterinary MedicineChina Agricultural UniversityBeijing 100193China College of Animal Science and Technology Henan Agricultural UniversityZhengzhou 450046China

Background Follicular atresia significantly impairs female fertility and hastens reproductive *** of granulosa cells is the primary cause of follicular *** and necroptosis,as additional forms of pro-grammed cell death,have been reported in mammalian ***,the understanding of pyroptosis and necrop-tosis pathways in granulosa cells during follicular atresia remains *** study explored the effects of pro-grammed cell death in granulosa cells on follicular atresia and the underlying *** The results revealed that granulosa cells undergo programmed cell death including apoptosis,pyroptosis,and necroptosis during follicular *** the first time,we identified the formation of a PANoptosome com-plex in porcine granulosa *** complex was initially identified as being composed of ZBP1,RIPK3,and RIPK1,and is recruited through the RHIM ***,we demonstrated that caspase-6 is activated and cleaved,interacting with RIPK3 as a component of the *** stress may exacerbate the activation of the PANop-tosome,leading to programmed cell death in granulosa *** Our data identified the formation of a PANoptosome complex that promoted programmed cell death in granulosa cells during the process of follicular *** findings provide new insights into the molecular mechanisms underlying follicular atresia.

关键词： Follicular atresia Granulosa cells PANoptosome Programmed cell death

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Seasonal influence on miRNA expression dynamics of extracellular vesicles in equine follicular fluid

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Journal of Animal Science and Biotechnology 2025年第1期16卷 136-152页

作者： Jean M.Feugang Ahmed Gad Nico G.Menjivar Ghassan M.Ishak Samuel Gebremedhn Melba O.Gastal Notsile H.Dlamini Radek Prochazka Eduardo L.Gastal Dawit Tesfaye Department of Animal and Dairy sciences Mississippi State UniversityMississippi StateMS 39762USA Animal Reproduction and Biotechnology Laboratory(ARBL) Department of Biomedical SciencesCollege of Veterinary Medicine and Biomedical SciencesColorado State UniversityFort CollinsCO 80523USA Department of Animal Production Faculty of AgricultureCairo UniversityGiza 12613Egypt Department of Surgery and Obstetrics College of Veterinary MedicineUniversity of BaghdadBaghdad 10011Iraq Animal Science School of Agricultural SciencesSouthern Illinois UniversityCarbondaleIL 62901USA J.R.Simplot Company KunaID 83634USA Institute of Animal Physiology and Genetics Czech Academy of SciencesLiběchov 27721Czech Republic

Background Ovarian follicular fluid(FF)is a dynamic environment that changes with the seasons,affecting follicle development,ovulation,and oocyte *** in the follicles release tiny particles called extracellular vesicles(EVs)containing vital regulatory molecules,such as microRNAs(miRNAs).These miRNAs are pivotal in facilitating commu-nication within the follicles through diverse signaling and information transfer ***-coupled miRNA signaling is implicated to be associated with ovarian function,follicle and oocyte growth and response to various environmen-tal ***,we investigated how seasonal variations directly influence the ovulatory and anovulatory states of ovarian follicles and how are they associated with follicular fluid EV-coupled miRNA dynamics in *** Ultrasonographic monitoring and follicular fluid aspiration of preovulatory follicles in horses during the ano-vulatory(spring:non-breeding)and ovulatory(spring,summer,and fall:breeding)seasons and subsequent EV isola-tion and miRNA profiling identified significant variation in EV-miRNA cargo *** identified 97 miRNAs with dif-ferential expression among the groups and specific clusters of miRNAs involved in the spring transition(miR-149,-200b,-206,-221,-328,and-615)and peak breeding period(including miR-143,-192,-451,-302b,-100,and let-7c).Bioinformatic analyses showed enrichments in various biological functions,e.g.,transcription factor activity,transcrip-tion and transcription regulation,nucleic acid binding,sequence-specific DNA binding,p53 signaling,and post-trans-lational *** analyses revealed distinct sets of significantly up-and down-regulated miRNAs associ-ated with spring anovulatory(Cluster 1)and summer ovulation–the peak breeding season(Clusters 4 and 6).Conclusions The findings from the current study shed light on the dynamics of FF-EV-coupled miRNAs in relation to equine ovulatory and anovulatory seasons,and their roles in understanding the

关键词： Extracellular vesicle Follicle growth Follicular fluid Horse Mare Ovulation Pre-ovulation Seasonal breeding

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Velogenic Newcastle disease virus invades chicken brain by infecting brain microvascular endothelial cells to increase blood-brain barrier permeability

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Journal of Integrative Agriculture 2025年第2期24卷 712-723页

作者： Jie Zhao Sa Xiao Wei Yao Xudong Chang Xinglong Wang Zengqi Yang Wenbin Wang Poultry Institute Shandong Academy of Agricultural Sciences College of veterinary Medicine Northwest A&F University People's Government of Guangpu Town

The blood-brain barrier(BBB) keeps poisons and infections out of the brain. Some viruses can pass through this barrier and replicate in the central nervous system(CNS). Velogenic Newcastle disease virus(VNDV) is a neurotropic virus that causes avian nonsuppurative encephalitis. VNDV often develops into a chronic infection that seriously affects poultry health in partially immune birds. The routes by which the virus enters the chicken brain are poorly understood. In this study, we discovered that VNDV increased BBB permeability in vivo and in vitro by breaking the tight junction protein zona occludens-1(ZO-1) continuity of chicken brain microvascular endothelial cells(chBMECs). By investigating the susceptibility of chBMECs to NDV infection, we found that VNDV but not lentogenic NDV was detected in the basolateral compartment in transwell assays after apical infection, suggesting that efficient replication and transcellular transport of the virus across the BBB in vitro. Furthermore, viral replication and BBB permeability were reduced during the early stage of infection by using the dynamin inhibitor dynasore. Our data demonstrate that VNDV invades the chicken brain by infecting and damaging the tight junction of chBMECs directly to increase BBB permeability. VNDV could infect chBMECs via endocytosis. As a result, our findings provide compelling evidence for VNDV entrance into the brain via the BBB, paving the way for the development of medications for NDV prevention and therapy.

关键词： velogenic Newcastle disease virus blood-brain barrier permeability chicken brain microvascular endothelial cells

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Deletion of Salmonella pathogenicity islands SPI-1, 2 and 3 induces substantial morphological and metabolic alternation and protective immune potential

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Journal of Integrative Agriculture 2025年第1期24卷 272-289页

作者： Gaosong Liu Xuelian Lü Qiufeng Tian Wanjiang Zhang Fei Yi Yueling Zhang Shenye Yu State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China

The Salmonella pathogenicity islands(SPIs) play crucial roles in the progression of Salmonella infection. In this study, we constructed an improved λ Red homologous recombination system to prepare single and triple deletion mutants of 3 prominent SPIs(SPI-1, 2, and 3), aiming at the impact of deletion on morphology, carbon source metabolism, adhesion and invasion capacity, in vivo colonization, and immune efficacy in chicks. Our examination revealed that the surface of the single deletion mutants(SM6ΔSPI1, ΔSPI2, and ΔSPI3) exhibited a more rugged texture and appeared to be enveloped in a layer of transparent colloid, whereas the morphology of the triple deletion mutant(SM6ΔSPI1&2&3) remained unaltered when compared to the parent strain. The carbon metabolic spectrum of the SPI mutants underwent profound alterations, with a notable and statistically significant modification observed in 30 out of 95 carbon sources, primarily carbohydrates(17 out of 30). Furthermore, the adhesion capacity of the 4 mutants to Caco-2 cells was significantly reduced when compared to that of the parent strain. Moreover,the invasion capacity of mutants SM6ΔSPI1 and SM6ΔSPI1&2&3 exhibited a substantial decrease, while it was enhanced to varying degrees for SM6ΔSPI3 and SM6ΔSPI2. Importantly, none of the 4 mutants induced any clinical symptoms in the chicks. However, they did transiently colonize the spleen and liver. Notably, the SM6ΔSPI1&2&3mutant was rapidly cleared from both the spleen and liver within 8 days post-infection and no notable pathological changes were observed in the organs. Additionally, when challenged, the mutants immunized groups displayed a significant increase in antibody levels and alterations in the CD3+CD4+ and CD3+CD8+ subpopulations, and the levels of IL-4 and IFN-γ cytokines in the SM6ΔSPI1&2&3 immunized chicken serum surpassed those of other *** summary, the successful construction of the 4 SPI mutants lays the groundwork for further exploration into the p

关键词： Salmonella pathogenicity islands(SPls) morphology carbon source metabolism pathogenicity immunogenicity live attenuated vaccine

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Selenium deficiency exacerbates ROS/ER stress mediated pyroptosis and ferroptosis induced by bisphenol A in chickens thymus

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Journal of Environmental sciences 2025年第2期148卷 13-26页

作者： Kun Wang Xu Shi Hongjin Lin Tong Xu Shiwen Xu College of veterinary Medicine Northeast Agricultural UniversityHarbin 150030China Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment Harbin 150030China

Bisphenol A(BPA)is an industrial pollutant that can cause immune *** acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ *** study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)*** established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 *** results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,*** vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ***,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.

关键词： Bisphenol A Selenium deficiency ROS/ER stress Pyroptosis Ferroptosis Thymic injury

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Unraveling the role of long non‑coding RNAs in chronic heat stress‑induced muscle injury in broilers

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Journal of Animal Science and Biotechnology 2025年第1期16卷 206-217页

作者： Zhen Liu Yingsen Liu Tong Xing Jiaolong Li Lin Zhang Liang Zhao Yun Jiang Feng Gao College of Animal Science and Technology Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu ProvinceJiangsu Collaborative Innovation Center of Meat Production and ProcessingQuality and Safety ControlNanjing Agricultural UniversityNanjing 210095People’s Republic of China Anhui Key Laboratory of Livestock and Poultry Product Safety Engineering Institute of Animal Husbandry and Veterinary MedicineAnhui Academy of Agricultural SciencesHefei 230031China Institute of Agro‑Products Processing Jiangsu Academy of Agricultural SciencesNanjing 210014People’s Republic of China School of Food Science and Pharmaceutical Engineering Nanjing Normal UniversityNanjing 210023People’s Republic of China

Background Chronic heat stress(CHS)is a detrimental environmental stressor with a negative impact on the meat quality of ***,the underlying mechanisms are not fully *** study investigates the effects of CHS on long non-coding RNA(lncRNA)expression and muscle injury in broilers,with a focus on its implications for meat *** The results showed that CHS diminished breast muscle yield,elevated abdominal fat deposition,induced cellular apoptosis(P<0.05),and caused *** analysis revealed 151 differentially expressed(DE)lncRNAs when comparing the normal control(NC)and HS groups,214 DE lncRNAs when comparing the HS and PF groups,and 79 DE lncRNAs when comparing the NC and pair-fed(PF)*** eliminating the confounding effect of feed intake,68 lncRNAs were identified,primarily associated with cellular growth and death,signal transduc-tion,and metabolic ***,the apoptosis-related pathway P53,lysosomes,and the fibrosis-related gene TGF-β2 were significantly upregulated by *** These findings indicate that chronic heat stress induces cellular apoptosis and muscle injury through lncRNA,leading to connective tissue accumulation,which likely contributes to reduced breast muscle yield and meat quality in broilers.

关键词： Apoptosis Broiler Chronic heat stress LncRNA Muscle

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Adjusting *CO adsorption configuration over tandem trimetallic AuAgCu heterojunction boosts CO_(2) electroreduction to ethanol via asymmetric C–C coupling

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Science China Materials 2025年第1期68卷 173-179页

作者： Yongxia Shi Junjun Li Zhiwen Min Xinyi Wang Man Hou Hao Ma Zechao Zhuang Yuchen Qin Yuanmiao Sun Dingsheng Wang Zhicheng Zhang Key Laboratory of Organic Integrated Circuit Ministry of Education&Tianjin Key Laboratory of Molecular Optoelectronic SciencesDepartment of ChemistrySchool of ScienceTianjin UniversityTianjin 300072China faculty of Materials Science and Energy Engineering/Institute of Technology for Carbon Neutrality Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Chemistry Tsinghua UniversityBeijing 100084China College of sciences Henan Agricultural UniversityZhengzhou 450000China

Rationally modulating the adsorption configuration of the key*CO intermediate could facilitate carbon±carbon(C±C)coupling to generate multi-carbon products in the electrochemical CO_(2) reduction *** this work,theoretical calculations reveal that C±C coupling via atopadsorbed*CHO and hollow-adsorbed*CO over Cu sites is an energetically favorable *** a proof of concept,a tandem trimetallic AuAgCu heterojunction(Au@Ag/Cu)was prepared,where the atop-adsorbed*CO over Au@Ag sites could migrate to Cu sites with hollow adsorption configuration,and then the asymmetric C±C coupling via transferred hollow-adsorbed*CO and existed atop-adsorbed*CHO over Cu sites facilitates the formation of the ethanol product,exhibiting a maximum Faraday efficiency of 65.9%at a low potential of−0.3 V *** hydrogen *** work provides new insights into the intrinsic understanding of tandem catalysis by regulating adsorption configuration of the intermediate products.

关键词： CO_(2)electroreduction C–C coupling tandem catalysis adsorption configuration ethanol

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Impact and zoning of production-living-ecological spaces changes on carbon balance:Evidence from Shandong province, China

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Journal of Geographical sciences 2025年第2期35卷 293-314页

作者： LIU Chao XU Yueqing JI Zhengxin College of Land Science and Technology China Agricultural University faculty of Political Science College of Public Administration Central China Normal University

Changes in production-living-ecological spaces(PLES) profoundly affect the global carbon cycle, further challenging socio-ecological system sustainability. However, the impacts of PLES changes on carbon balance have been insufficiently discussed under a spatial heterogeneity perspective, resulting in an inadequate understanding of green development. This paper quantified the dynamics of PLES using the transfer matrix method and assessed the carbon balance computed by the ecological support coefficient of carbon emissions(ESC) in Shandong province from 2000 to 2020. The impacts of PLES changes on ESC were further investigated using a geographically weighted regression model. On this basis, carbon balance zones were delineated through cluster analysis. The results indicated that both production and ecological spaces decreased while the living space increased during 2000–2020. Carbon emissions increased and its sequestration decreased. As a result, ESC initially increased and then decreased, exhibiting apparent spatial clustering. The impact of different PLES transfer changes on ESC varies across county sites, with production→living space having the most significant impact on regional ESC and ecology→living space having the most negligible impact. Finally, six types of carbon balance zones were established to reduce carbon emissions. The findings are expected to support policy implementations for reducing carbon emissions and optimizing territorial development through low-carbon land use.

关键词： carbon emission carbon sequestration land use spatial heterogeneity Shandong province

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Emerging patterns of antimicrobial resistance:Concurrent presence of mcr-1.1 and mcr-8.1 in a ST15 Klebsiella pneumoniae isolated from poultry in China

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Journal of Integrative Agriculture 2025年第1期24卷 403-407页

作者： Dong'an Cui Panpan Liu Ling Wang Jiongjie He Yuzhang Yan Mengke Ru Baocheng Hao Yan Sun Shengyi Wang Key Laboratory of New Animal Drug Project Gansu Province/Key Laboratory of Veterinary Pharmaceutical DevelopmentMinistry of Agriculture and Rural AffairsLanzhou Institute of Husbandry and Pharmaceutical SciencesChinese Academy of Agricultural SciencesLanzhou 730050China College of Animal Science and Technology Guangxi UniversityNanning 530005China China Institute of veterinary Drug Control Beijing 100081China

Colistin serves as a crucial treatment for multidrugresistant(MDR)Gram-negative bacterial ***,its excessive use has contributed to an increase in colistin-resistant strains within livestock production(Binsker et al.2022).The mobile colistin resistance gene,mcr,which reduces colistin affinity by incorporating phosphoethanolamine(pEtN)into the bacterial lipopolysaccharide,significantly compromises the effectiveness of colistin treatments(Liu et al.2016).

关键词： poultry treatment compromise

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