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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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Molecular breakthroughs in modern plant breeding techniques

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Horticultural Plant Journal 2025年第1期11卷 15-41页

作者： Mughair Abdul Aziz Khaled Masmoudi Department of Integrative Agriculture College of Agriculture and Veterinary MedicineUnited Arab Emirates UniversityAl-AinAbu-DhabiUnited Arab Emirates

Advancements in molecular approaches have been utilized to breed crops with a wide range of economically valuable traits to develop superior *** review provides a concise overview of modern breakthroughs in molecular plant *** and high-throughput phenotyping methods for predictive plant breeding are briefly *** this study,we explore contemporary molecular breeding techniques for producing desirable crop *** techniques include cisgenesis,clustered regularly interspaced short palindromic repeat(CRISPR/Cas9)gene editing,haploid induction,and de novo *** examine the speed breeding approach-a strategy for cultivating plants under controlled *** further highlight the significance of modern breeding technologies in efficiently utilizing agricultural resources for crop production in urban *** deciphering of crop genomes has led to the development of extensive DNA markers,quantitative trait loci(QTLs),and pangenomes associated with various desirable crop *** shift to the genotypic selection of crops considerably expedites the plant breeding *** on the plant population used,the connection between genotypic and phenotypic data provides several genetic elements,including genes,markers,and alleles that can be used in genomic breeding and gene *** integration of speed breeding with genomic-assisted breeding and cutting-edge genome editing tools has made it feasible to rapidly manipulate and generate multiple crop cycles and accelerate the plant breeding *** in molecular techniques have led to substantial improvements in modern breeding methods.

关键词： Plant breeding Molecular approaches Genotype Phenotype Crop traits

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Hunting for a viral proxy in bioaerosols of swine buildings using molecular detection and metagenomics

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Journal of Environmental Sciences 2025年第2期148卷 69-78页

作者： Valérie Létourneau Marie-Josée Gagné Jonathan M.Vyskocil Vincent Brochu Kim Robitaille Martin Gauthier Julie Brassard Caroline Duchaine Quebec Heart and Lung Institute Research centre-UniversitéLaval 2725 Chemin Sainte-FoyQuebecG1V 4G5Canada Saint-Hyacinthe Research and Development centre Agriculture and Agri-Food Canada3600 Casavant Boulevard WestSaint-HyacintheJ2S 8E3Canada Department of Biochemistry Microbiologyand Bio-informaticsFaculty of Science and EngineeringUniversitéLaval1045 Avenue de la MédecineQuebecG1V 0A6Canada The Swine and Poultry Infectious Diseases Research centre Faculty of Veterinary Medicine of Universitéde Montréal3200 Rue SicotteSaint-HyacintheJ2S 2M2Canada

There are limited biosecurity measures directed at preventing airborne transmission of viruses in *** effectiveness of dust mitigation strategies such as oil sprinkling,to decrease risk of airborne virus transmission are *** and qPCR for common fecal viruses were used to hunt for a ubiquitous virus to serve as a proxy when evaluating the efficiency of mitigation strategies against airborne viral infectious *** particles were collected from swine buildings using high-volume air *** DNA and RNA were used to perform specific RT-qPCR and qPCR and analyzed by highthroughput *** astroviruses group 2 were common(from 102 to 105 genomic copies per cubic meter of air or gc/m^(3),93%positivity)while no norovirus genogroup II was recovered from air *** torque teno sus virus were detected by qPCR in low concentrations(from 101 to 102 gc/m^(3),47%positivity).Among the identified viral families by metagenomics analysis,Herelleviridae,Microviridae,Myoviridae,Podoviridae,and Siphoviridae were *** phage vB_AviM_AVP of Aerococcus was present in all air samples and a newly designed qPCR revealed between 101 and 105 gc/m^(3) among the samples taken for the present study(97%positivity)and banked samples from5-and 15-year old studies(89%positivity).According to the present study,both the porcine astrovirus group 2 and the phage vB_AviM_AVP of Aerococcus could be proxy for airborne viruses of swine buildings.

关键词： Bioaerosols Viral metagenomics Astrovirus Aerococcus phage Swine buildings

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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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Immortalization of epidural fat-derived mesenchymal stem cells: In vitro characterization and adipocyte differentiation potential

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World Journal of Stem Cells 2025年第1期17卷 40-52页

作者： Seoung-Woo Lee Young-Ju Lim Hee-Yeon Kim Wansoo Kim Wook-Tae Park Min-Jung Ma Junho Lee Min-Soo Seo Young In Kim Sangbum Park Seong-Kyoon Choi Gun Woo Lee Core Protein Resources Center Daegu-Gyeongbuk Institute of Science and TechnologyDaegu 42988South Korea Department of Orthopedic Surgery Yeungnam University Medical CenterYeungnam University College of MedicineDaegu 42415South Korea Department of veterinary Pathology College of Veterinary MedicineKyungpook National UniversityDaegu 41566South Korea School of Life Science BK21 FOUR KNU Creative BioResearch GroupKyungpook National UniversityDaegu 41566South Korea Laboratory of veterinary Tissue Engineering College of Veterinary MedicineKyungpook National UniversityDaegu 41566South Korea College of veterinary Medicine Kyungpook National UniversityDaegu 41566South Korea Department of veterinary Tissue Engineering Kyungpook National UniversityDaegu 41566South Korea Cellexobio. Ltd.Daegu 42415South Korea Michigan State University Institute for Quantitative Health Science&EngineeringEast LansingMI 48824United States Department of Orthopedic Surgery Yeungnam University College of MedicineDaegu 42415South Korea

BACKGROUND Mesenchymal stem cells(MSCs)are promising candidates for regenerative therapy due to their self-renewal capability,multilineage differentiation potential,and immunomodulatory *** molecular characteristics of MSCs are influenced by their ***,epidural fat(EF)and EF-derived MSCs(EF-MSCs)have garnered attention due to their potential benefits to the spinal microenvironment and their high expression of neural SC ***,their clinical applications are limited due to cell senescence and limited accessibility of *** many studies have attempted to establish an immortalized,stable SC line,the characteristics of immortalized EF-MSCs remain to be *** To establish and analyze stable immortalized *** The phenotypes of EF-MSCs were analyzed using optical *** immortalization was performed using lentiviral *** biomolecular characteristics of the cells were analyzed by immunoblotting,quantitative PCR,and *** The immortalized EF-MSCs demonstrated a significantly extended lifespan compared to the control group,with well-preserved adipogenic potential and SC surface marker *** of human telomerase reverse transcriptase genes markedly increased the lifespan of *** analysis revealed substantial increase in the expression of DNA replication pathway components in immortalized *** Immortalized EF-MSCs exhibited significantly enhanced proliferative capacity,retained adipogenic potential,and upregulated the expression of DNA replication pathway components.

关键词： Immortalization Transfection Stem cell Epidural fat Proteomics

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A study on antimicrobial effect of sugars at low concentration

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Infectious Diseases Research 2025年第1期6卷 1-9页

作者： Bhoj Raj Singh Mudit Chandra Monika Bhardwaj Varsha Jayakumar Akhilesh Kumar Division of Epidemiology ICAR-Indian Veterinary Research InstituteIzatnagar 243122India Department of veterinary Microbiology College of Veterinary SciencesGuru Angad Dev Veterinary and Animal Sciences UniversityLudhianaPunjab 141012India Department of veterinary Microbiology Dr.G.C.Negi College of Veterinary and Animal SciencesChaudhary Sarwan Kumar Himachal Pradesh Krishi VishvavidyalayaPalmapur 176062India Division of veterinary Medicine ICAR-Indian Veterinary Research InstituteIzatnagar 243122India

Background:Although many sugars are known antibacterial in higher concentrations(>50%W/V)and a few at low concentrations too(≤1 mg/mL),most of the studies are limited to only a few reference isolates,therefore no concrete conclusion can be ***:This study evaluated the antimicrobial potential of 19 sugars against 8000 isolates of bacteria belonging to 46 genera and also against 30 reference strains of microbes of 14 different *** determine susceptibility to sugars,a sugar-disc(1 mg)diffusion assay was performed on Mueller Hinton agar using the same method used for antimicrobial susceptibility of microbial ***:In the study,of 3,336 isolates of Gram-positive bacteria 147(4.35%)were susceptible to one or more sugars but only 16(0.37%)of the 4644 isolates of Gram-negative bacteria were susceptible to one or other ***-positive bacteria were significantly more often susceptible to one or more sugars than isolates of Gram-negative bacteria(OR 13.33,CI99,6.74–26.37).A total of 163 test-isolates(2.04%)but none of the reference strains were sugar *** of the isolates susceptible to sugars(135 of 2,295)were members of the Bacillaceae(36/679)and Micrococcaceae(99/1,616)***,out of 5,705 isolates belonging to other bacterial families,only 28 isolates(0.49%)were susceptible to one or more *** most effective to least effective sugars as antibacterial were mannose,inositol,mannitol,sucrose,raffinose,ribose,xylose,trehalose,dulcitol,maltose,lactose,inulin,salicin,melibiose,sorbitol,adonitol,arabinose,glucose,and esculin,inhibiting 69,58,23,14,11,10,10,7,7,7,6,6,5,5,5,5,2,1,and 1 of the test-isolates,***:The results are still intriguing in determining the utility of sugar susceptibility of different bacteria and are still beyond making any conclusion for their therapeutic ***,the study can be concluded that Gram-positive bacteria are generally more susceptible to lower concentrations of di

关键词： Enterobacteriaceae Bacillaceae Enterococcaceae Streptococcaceae Aeromonadaceae mannose inositol mannitol

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Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri H.Juárez Adalberto Merighi Department of veterinary Sciences University of TurinGrugliascoTOItaly Department of Psychiatry and Neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical *** have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue *** enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC *** increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

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Sero-Prevalence of Peste des Petits Ruminants Virus Antibodies in Sudanese Sheep and Goats before and after Vaccination

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Journal of Biosciences and Medicines 2025年第1期13卷 21-40页

作者： Omer Algezoli Selma Kamal Yazeed Raouf Alamin Mozdalifa Hiba Ali Mohamed Aljameel Salih Sir Elkhatim Sulieman Ahmed Ibtesam Fadul Elsied Tageldin Nour Mohamed Abdalla Viral Vaccine Production Department Central Veterinary Research Laboratory Khartoum Sudan College of veterinary Medicine Sudan University of Science and Technology Khartoum-North Sudan Epidemiology Department Central Veterinary Research Laboratory Khartoum Sudan Foot and Mouth Disease Department Central Veterinary Research Laboratory Khartoum Sudan Virology Department Central Veterinary Research Laboratory Khartoum Sudan Nyala veterinary Research Laboratory Nyala Sudan Damazine veterinary Research Laboratory Damazine Sudan Al Obeid veterinary Research Laboratory Al Obeid Sudan

Peste des petits ruminants virus (PPRV) antibodies were studied in Sudanese sheep and goats (n = 855) before and after vaccination with a locally produced Nigeria 75/1 vaccine using a commercial competitive ELISA (cELISA) kit. Animals were kept healthy under field conditions, in four states: Blue Nile (n = 250), North Kordofan (n = 189), South Darfur (n = 225) and the Northern State (n = 191). Before vaccination, the overall sero-prevalence of PPRV antibodies was 54.6% (53.2% - 56%, 95% CI);high (64.8% - 76.4%, 95% CI) in Blue Nile State, medium (50.5% - 61.9%, 95% CI) in North Kordofan State and South Darfur State and low (28.6% - 35.2% 95%, CI) in Northern State. In high-risk areas (high sero-prevalence), Blue Nile (70.4%) and North Kordofan (57.7%), middle age groups (7 - 12 and 13 - 18 months) were identified as high-risk age. Middle age groups showed lower sero-prevalence than preceding (3 - 6 months) and subsequent (>18 months) age groups while the risk of exposure increased with age. Current and previous findings suggested a transmission pathway of PPRV involving the South Eastern border (Blue Nile) and neighbouring Central Sudan to North Kordofan. One month after vaccination 88.4% (343/388) of sero-negative animals were sero-converted suggesting the efficacy of the locally produced Nigeria 75/1 vaccine. Even if only individuals in the high-risk age group (7 - 18 months) were vaccinated, the overall population immunity (OPI) in high-risk areas (the Blue Nile and North Kordofan) would have surpassed the threshold of 70%, which is indicated for blocking PPRV transmission. However, lower vaccination coverage is expected in wider vaccination programmes. These findings primarily justified the targeting of PPR control in Sudan through the vaccination of high-risk age groups in high-risk areas.

关键词： Peste des Petits Ruminants (PPR) Vaccination Efficacy Seroprevalence Herd Immunity High-Risk Area

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Optimization and Scaling-Up of Peste des Petits Ruminants (PPR) Vaccine Production Using Roller Bottle Platform

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Journal of Biosciences and Medicines 2025年第1期13卷 378-393页

作者： Omer Algezoli Tagelden Nour Muzdalifa Alamin Mohamed Abdalla Central veterinary Research Laboratory Khartoum Sudan College of veterinary Medicine Sudan University of Science and Technology Khartoum-North Sudan

Peste des Petits ruminants (PPR) is considered as one of the major constraints to the productivity of small ruminants in Sudan. Presently, control measures for PPR are primarily reliant on vaccination using an attenuated PPR strain Nigeria 75/1 that has been produced in monolayers of Vero cells grown in static flasks. This study investigates the potential for scaling up PPR vaccine production using roller bottle technology, a more advanced method. A live, homologous vaccine against PPR in sheep and goats was successfully produced on a large scale in roller culture bottles, with DMEM supplemented with ten percent fetal bovine serum serving as the growth medium. The cells were infected with a multiplicity of infection of 0.01, and the vaccine was harvested when the cytopathic effect reached 80%. The vaccine was then freeze-dried to preserve its stability. A series of tests were conducted to ensure the safety and quality of the vaccine. Using PCR, the identity of vaccine was confirmed. It was found to be safe in both single and 100-times dose inoculations in sheep, with the produced batches showing a high titre of 6.4 ± 0.11 log10 TCID50/ml. All batches met the criteria of sterility, passing tests for bacteria, fungi, and mycoplasma. Furthermore, the vaccine proved effective in small ruminants, with antibodies persisting for over a year post-vaccination. The residual moisture content remained below 2.5%, and the vaccine successfully passed vacuum testing. Stability tests indicated that the vaccine has a shelf-life of at least one year when stored at temperatures of 2˚C - 8˚C and −20˚C. These results demonstrate the potential for applying roller bottle culture technology to PPR vaccine production, significantly streamlining the existing process and enhancing its efficiency. Further research is warranted to address the economic analyses of adopting roller bottle technology with existing PPR control program.

关键词： Large-Scale Production Pest des Petits Ruminants Roller Bottle Technology Vaccination Vero Cell

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From mice to humans:a need for comparable results in mammalian neuroplasticity

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Neural Regeneration Research 2025年第2期20卷 464-466页

作者： Marco Ghibaudi Enrica Boda Luca Bonfanti Neuroscience Institute Cavalieri Ottolenghi OrbassanoItaly Department of veterinary Sciences University of TurinTurinItaly Department of Neuroscience Rita Levi-Montalcini University of TurinTurinItaly

Brain plasticity-A universal tool with many variations:The study of brain plasticity has been gaining interest since almost a century and has now reached a huge amount of information(>80,000 results in PubMed).Overall,different types of plasticity,including stem cell-driven genesis of new neurons(adult neurogenesis),cells in arrested maturation(dormant neurons),neuro-glial and synaptic plasticity,can coexist and contribute to grant plastic changes in the brain,from a cellular to system level(Benedetti and Couillard-Despres,2022;Bonfanti et al.,2023).

关键词： plasticity al. arrest

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