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Assessment of the piroxicam-incited model of synchronized colitis in T-cell receptor alpha chain-deficient mice

Animal Models and Experimental Medicine 2024年第4期7卷 533-543页

作者： Maximo E.Lange Danisa M.Bescucci Valerie F.Boras Tony Montina G.Douglas Inglis douglas inglis 11 lethbridge research and development centre agriculture and agri-food canadalethbridgealbertacanada alberta health services chinook regional hospitallethbridgealbertacanada department of chemistry and biochemistry university of lethbridgelethbridgealbertacanada southern alberta genome sciences centre university of lethbridgelethbridgealbertacanada

Background:A multitude of mouse models are utilized to emulate and study intestinal inflammation.T-cell receptor alpha chain(TCRα)-deficient mice are used as a model of spontaneous colitis that has similarities with human ulcerative ***,colitis is triggered late in the life of the mouse(age:4-5 months),and inflammation does not develop at the same time in different mice.A previously conducted study reported that the administration of the drug piroxicam triggered predictable and early colitis in TCRα-deficient mice at the age of 6-8 ***,a detailed characterization of ensuing inflammation was not ***:We conducted an in-depth examination of piroxicam-triggered colitis in TCRα-deficient mice,with emphasis on spatial histopathologic changes and analysis of expression of inflammatory ***,we tested amelioration of colitis with ***:We confirmed that piroxicam induced a time-prescribed colitis and did so in the proximal colon as well as the cecum of TCRα-deficient *** adminis-tration was observed to induce epithelial hyperplasia,goblet cell loss,and leukocyte infiltration with occasional ulceration.A Swiss roll technique was used to examine the colon and cecum in its ***,we observed that inflammation was mul-tifocal segmental,with areas of tissue damage in between healthy *** addition,we observed variability in the severity of inflammation among replicate animals and treatments,and that the administration of dexamethasone only partially ameliorated inflammation in the proximal ***:Piroxicam consistently induced multifocal segmental colitis in the proxi-mal colon and cecum,although the degree of inflammation was reduced in the ***,spatial variability in inflammation in the large intestine and the inter-replicate variation in the severity of inflammation must be taken into consideration when utilizing this murine model of synchronized colitis.

关键词： colon dexamethasone histology induction inflammation knockout

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Engineered extracellular vesicles efficiently deliver CRISPR-Cas9 ribonucleoprotein(RNP)to inhibit herpes simplex virus1 infection in vitro and in vivo

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1362-1379页

作者： Yuanda Wan Liren Li Ruilin Chen Jiajia Han Qiyun Lei Zhipeng Chen Xiaodong Tang Wenyu Wu Shuwen Liu Xingang Yao NMPA Key Laboratory for Research and Evaluation of Drug Metabolism Guangdong Provincial Key Laboratory of New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Center of Clinical Pharmacy Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Key Laboratory of Infectious Diseases Research in South China(southern Medical University) Ministry of EducationGuangzhou 510515China

Extracellular vesicles(EVs)have recently emerged as a promising delivery platform for CRISPR/Cas9 ribonucleoproteins(RNPs),owing to their ability to minimize off-target effects and immune ***,enhancements are required to boost the efficiency and safety of Cas9 RNP enrichment within *** response,we employed the Fc/Spa interaction system,in which the human Fc domain was fused to the intracellular domain of PTGFRN-Δ687 and anchored to the EV ***,the B domain of the Spa protein was fused to the C domain of cargos such as Cre or *** to the robust interaction between Fc and Spa,this method enriched nearly twice the amount of cargo within the *** loaded with spCas9 RNP targeting the HSV1 genome exhibited significant inhibition of viral replication in vitro and in ***,following neuron-targeting peptide RVG modification,the in vivo dosage in neural tissues substantially increased,contributing to the clearance of the HSV1 virus in neural tissues and exhibiting a lower off-target *** findings establish a robust platform for efficient EV-based SpCas9 delivery,offering potential therapeutic advantages for HSV1 infections and other neurological disorders.

关键词： Extracellular vesicles CRISPR/Cas9 Ribonucleoproteins PTGFRN Fc/Spa HSV1 Neuron-targeting Delivery

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Structural basis for polyuridine tract recognition by SARS-CoV-2 Nsp15

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Protein & Cell 2024年第7期15卷 547-552页

作者： Fumiaki Ito Hanjing Yang Z.Hong Zhou Xiaojiang S.Chen Molecular and Computational Biology Department of Biological SciencesUniversity of Southern CaliforniaLos AngelesCA 90089United States Department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos AngelesCA 90095United States California NanoSystems Institute University of CaliforniaLos AngelesCA90095United States Genetic Molecular and Cellular Biology ProgramKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90089United States Norris Comprehensive Cancer Center University of Southern CaliforniaLos AngelesCA 90089United States Center of Excellence in NanoBiophysics University of Southern CaliforniaLos AngelesCA 90089United States

Dear Editor,Coronaviruses have evolved a wide array of tactics to evade host antiviral *** host cells detect invading foreign nucleic acids including viral genome and viral replication intermediates,they activate interferon(IFN)signaling via cytoplasmic pattern recognition receptors(Kang et al.,2002;Kato et al.,2006).Remarkable stealth activities exhibited by coronaviruses are facilitated by a series of non-structural proteins(Nsps),such as Nsp15(Deng and Baker,2018;Deng et al.,2019;Hackbart et al.,2020),which is a uridine-specific endoribonuclease that mediates evasion of host detection of viral double-stranded RNA(dsRNA)(Bhardwaj et al.,2004;Deng et al.,2017;Frazier et al.,2021;Ivanov et al.,2004).Nsp15 targets a polyuridine[poly(U)]tract on the coronavirus negative strand RNA(Hackbart et al.,2020).Nsp15 limits the abundance and length of poly(U)within the negative strand RNA 5ʹ-extension by trimming down the initially synthesized poly(U)lead sequence to the optimal length that can suppress dsRNA formation but still serves as a template for poly(A)tail of the positive strand genome of the coronaviruses(Hofmann and Brian,1991).

关键词： p15 interferon template

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Genomic insights into adaptation to bipedal saltation and desert-like habitats of jerboas

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Science China(Life sciences) 2024年第9期67卷 2003-2015页

作者： Simin Chai Yujie Chong Daiqing Yin Qiang Qiu Shixia Xu Guang Yang southern Marine Science and Engineering Guangdong Laboratory(Guangzhou) Guangzhou 511458China Jiangsu Key Laboratory for Biodiversity and Biotechnology School of Life SciencesNanjing Normal UniversityNanjing 210023China School of Ecology and Environment Northwestern Polytechnical UniversityXi’an 710072China

Jerboas is a lineage of small rodents displaying atypical mouse-like morphology with elongated strong hindlimbs and short *** have evolved obligate bipedal saltation and acute senses,and been well-adapted to vast desert-like *** a newly sequenced chromosome-scale genome of the Mongolian five-toed jerboa(Orientallactaga sibirica),our comparative genomic analyses and in vitro functional assays showed that the genetic innovations in both protein-coding and non-coding regions played an important role in jerboa morphological and physiological ***-specific amino acid substitutions,and segment insertions/deletions(indels)in conserved non-coding elements(CNEs)were found in components of proteoglycan biosynthesis pathway(XYLT1 and CHSY1),which plays an important role in limb ***,we found specific evolutionary changes functionally associated with energy or water metabolism(e.g.,specific amino acid substitutions in ND5 and indels in CNEs physically near ROR2)and senses(e.g.,expansion of vomeronasal receptors and the FAM136A gene family)in *** dual-luciferase reporter assay verified that some of the CNEs with jerboa-specific segment indels exerted a significantly different influence on luciferase activity,suggesting changes in their regulatory function in *** results revealed the potential molecular mechanisms underlying jerboa adaptation since the divergence from the Eocene-Oligocene transition,and provided more resources and new insights to enhance our understanding of the molecular basis underlying the phenotypic diversity and the environmental adaptation of mammals.

关键词： jerboa adaptive evolution comparative genomics conserved non-coding elements bipedal saltation

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Climate refugia along Lake Superior’s shores:disjunct arctic-alpine plants rely on cool shoreline temperatures but are restricted to highly exposed habitat under climate warming

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Journal of Plant Ecology 2024年第4期17卷 23-41页

作者： Ashley Hillman Scott E.Nielsen Department of Renewable Resources University of AlbertaEdmontonAB T6G 2R3Canada

Climate refugia can serve as a remnant habitat or stepping stones for species dispersal under climate *** largest freshwater lake by surface area,Lake Superior,USA and Canada,serves as a model system for understanding cooling-mediated local refugia,as its cool water temperatures and wave action have maintained shoreline habitats suitable for southern disjunct populations of arctic-alpine plants since ***,we seek to explain spatial patterns and environmental drivers of arctic-alpine plant refugia along Lake Superior’s shores,and assess future risk to refugia under moderate(+3.5℃)and warmest(+5.7℃)climate warming ***,we examined how the interactive effects of summer surface water temperatures and wind affected onshore temperatures,resulting in areas of cooler ***,we developed an ecological niche model for the presence of disjunct arctic-alpine refugia(pooling 1253 occurrences from 58 species)along the lake’s ***,we fit species distribution models for 20 of the most common arctic-alpine disjunct species and predicted presence to identify refugia ***,we used the two climate warming scenarios to predict changes in the presence of refugia and disjunct *** type,elevation above water,inland distance,July land surface temperature from MODIS/Terra satellite and near-shore depth of water were the best predictors of disjunct ***,we predicted 2236 km of the shoreline(51%)as disjunct refugia habitat for at least one species under current conditions,but this was reduced to 20% and 7% with moderate(894 km)and warmest(313 km)climate change projections.

关键词： climate refugia disjunct populations lake effect Lake Superior species distribution models

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The first mitogenome of Lauraceae(Cinnamomum chekiangense)

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Plant Diversity 2024年第1期46卷 144-148页

作者： Changwei Bi Ning Sun Fuchuan Han Kewang Xu Yong Yang David K.Ferguson State Key Laboratory of Tree Genetics and Breeding Co-Innovation Center for Sustainable Forestry in Southern ChinaKey Laboratory of Tree Genetics and Biotechnology of Educational Department of ChinaKey Laboratory of Tree Genetics and Silvicultural Sciences of Jiangsu ProvinceNanjing Forestry UniversityNanjing 210037China College of Information Science and Technology Nanjing Forestry UniversityNanjing 210037China Research Institute of Subtropical Forestry Chinese Academy of ForestryHangzhou 311400China Co-Innovation Center for Sustainable Forestry in southern China College of Life SciencesNanjing Forestry UniversityNanjing 210037China Department of Paleontology University of ViennaViennaAustria

There are three distinct genetic systems in higher plants,the dominant nuclear genome and the semi-autonomous organelle genomes(plastids and mitochondria).In contrast to the conserved plastid genome(plastome),the plant mitochondrial genome(mitogenome)is characterized by an intriguing“evolutionary paradox”distinguished by a remarkably low mutation rate but with a significantly high rearrangement rate(Palmer and Herbon,1988;Lai et al.,2022).

关键词： autonomous distinguished Palmer

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Knockout of miR396 genes increases seed size and yield in soybean

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Journal of Integrative Plant Biology 2024年第6期66卷 1148-1157页

作者： Hongtao Xie Fei Su Qingfeng Niu Leping Geng Xuesong Cao Minglei Song Jinsong Dong Zai Zheng Rui Guo Yang Zhang Yuanwei Deng Zhanbo Ji Kang Pang Jian‐Kang Zhu Jianhua Zhu School of Life sciences Anhui Agricultural UniversityHefei 230036China Research Center for Biological Breeding Technology Research Institute of Frontier ScienceAnhui Agricultural UniversityHefei 230036China Bellagen Biotechnology Co.Ltd Jinan 250000China Institute of Crop sciences/National Nanfan Research Institute Chinese Academy of Agricultural SciencesKey Laboratory of Gene Editing Technologies(Hainan)Ministry of Agriculture and Rural AffairsSanya 572025China southern University of Science and TechnologyShenzhen 518055China Hainan Yazhou Bay Seed Laboratory Sanya 572024China

Yield improvement has long been an important task for soybean breeding in the world in order to meet the increasing demand for food and animal *** R396 genes have been shown to negatively regulate grain size in rice,but whether mi R396 family members may function in a similar manner in soybean is ***,we generated eight soybean mutants harboring different combinations of homozygous mutations in the six soybean mi R396genes through genome editing with clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated nuclease(Cas)12SF01 in the elite soybean cultivar Zhonghuang 302(ZH302).Four triple mutants(mir396aci,mir396acd,mir396adf,and mir396cdf),two quadruple mutants(mir396-abcd and mir396acfi),and two quintuple mutants(mir396abcdf and mir396bcdfi)were *** found that plants of all the mir396 mutants produced larger seeds compared to ZH302 *** tests showed that mir396adf and mir396cdf plants have significantly increased yield in growth zones with relatively high latitude which are suited for ZH302 and moderately increased yield in lower *** contrast,mir396abcdf and mir396bcdfiplants have increased plant height and decreased yield in growth zones with relatively high latitude due to lodging issues,but they are suited for low latitude growth zones with increased yield without lodging *** together,our study demonstrated that loss-of-function of mi R396 genes leads to significantly enlarged seed size and increased yield in soybean,providing valuable germplasms for breeding high-yield soybean.

关键词： Cas12SF01 CRISPR/Cas miR396 seed size soybean yield

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Exploring biofilm-forming molecular determinants in Listeria monocytogenes by comparative genome-wide and transcriptomic analyses

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Food Science and Human Wellness 2024年

作者： Xinyi Zhang Changzheng Shi Zhaoxin Lu Fanqiang Meng Moutong Chen Xiaomei Bie College of Food Science and Technology， Nanjing Agricultural University Guangdong Provincial Key Laboratory of Microbial Safety and Health， State Key Laboratory of Applied Microbiology southern China， Institute of Microbiology， Guangdong Academy of sciences

In the food industry， bacterial cells usually adhere to equipment surfaces， forming biofilms that may cause persistent contamination. This study aimed to identify the key genes responsible for the stronger biofilm-forming capability of the LMB 33426 strain compared to that of the CICC 21662 strain through comparative genomics. Additionally， the expression of genes and related metabolic pathways of LMB 33426 and CICC 21662 strains were analyzed at the transcriptional level by high-throughput sequencing technology to uncover key differentially expressed genes between planktonic and biofilm cells of those two strains. Subsequently， the key genes found to present differences that were uncovered by those genome-wide and transcriptomic analyses were used to construct gene deletion strains. The crystalline violet assay and motility assay showed that GL002291， GL002712 and lmo1438 genes were involved in the regulation of biofilm formation as well as motility. The hydrophobicity and auto-aggregation ability assay results demonstrated an association between the clpB， lmo1438， and lmo0294 genes and bacterial adhesion. However， no significant differences were found regarding this association in the GL002291 and GL002712 genes. This study elucidates some potential regulatory genes associated with biofilm formation in L. monocytogenes， and laying a theoretical foundation for future research.

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The UDP-glycosyltransferase OsUGT706D2 positively regulates cold and submergence stress tolerance in rice

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The Crop Journal 2024年第3期12卷 732-742页

作者： Qing Liu Lanlan Zhang Shuwei Lyu Hang Yu Wenjie Huang Liqun Jiang Jing Zhang Bingrui Sun Xingxue Mao Pingli Chen Junlian Xing Wenfeng Chen Zhilan Fan Shijuan Yan Chen Li Guangdong Key Laboratory of New Technology in Rice Breeding/Guangdong Rice Engineering Laboratory/Key Laboratory of Genetics and Breeding of High Quality Rice in southern China(Co-construction by Ministry and Province) Ministry of Agriculture and Rural AffairsRice Research InstituteGuangdong Academy of Agricultural SciencesGuangzhou 510640GuangdongChina Guangdong Key Laboratory for Crop Germplasm Resources Preservation and Utilization Agro-biological Gene Research CenterGuangdong Academy of Agricultural SciencesGuangzhou 510640GuangdongChina

In a genome-wide association study,we identified a rice UDP-glycosyltransferase gene,OsUGT706D2,whose transcription was activated in response to cold and submergence stress and to exogenous abscisic acid(ABA).OsUGT706D2 positively regulated the biosynthesis of tricin-4’-O-(syringyl alcohol)ether-7-O-glucoside at both the transcriptional and metabolic ***706D2 mediated cold and submergence tolerance by modulating the expression of stress-responsive genes as well as the abscisic acid(ABA)signaling *** of function of OsUGT706D2 increased cold and submergence tolerance and loss of function of OsUGT706D2 reduced cold *** positively regulated OsUGT706D2-mediated cold tolerance but reduced submergence *** findings suggest the potential use of OsUGT706D2 for improving abiotic stress tolerance in rice.

关键词： UDP-glycosyltransferase Rice Cold tolerance Submergence tolerance ABA

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Efficient and multiplex gene upregulation in plants through CRISPR-Cas-mediated knockin of enhancers

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Molecular Plant 2024年第9期17卷 1472-1483页

作者： Qi Yao Rundong Shen Yang Shao Yifu Tian Peijin Han Xuening Zhang Jian-Kang Zhu Yuming Lu Shanghai Collaborative Innovation Center of Agri-Seeds Joint Center for Single-Cell BiologySchool of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China Shanghai Center for Plant Stress Biology Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghai 201602China University of the Chinese Academy of sciences BeijingChina College of Plant Science and Technology Huazhong Agricultural UniversityWuhan 430070China institute of Advanced Biotechnology and School of Medicine Southern University of Science and TechnologyShenzhen 518055China

Geneupregulation through genome editing is important for plant research and *** insertion of short transcriptional enhancers(STEs)into gene promoters may offer a universal solution akin to transgene-mediated overexpression while avoiding the drawbacks associated with ***,we introduce an“in locus activation”technique in rice that leverages well-characterized STEs for refined,heritable,and multiplexed gene *** address the scarcity of potent enhancers,we developed a large-scale mining approach and discovered a suite of STEs that are capable of enhancing gene expression in rice *** in locus integration of these STEs into eight rice genes resulted in substantial tran-scriptional upregulation in the edited plants,with up to 869.1-fold increases in their transcript ***-ploying a variety of STEs,we achieved delicate control of gene expression,enabling the fine-tuning of key phenotypic traits such as plant *** approach also enabled efficient multiplexed gene upregu-lation,with up to four genes activated simultaneously,significantly enhancing the nicotinamide mononucleotide metabolic ***,heritability studies from the To to T3 generations confirmed the stable and heritable nature of STE-driven gene ***,our work demon-strates that coupled with STE mining,leveraging genome editing for in locus activation and gene upregu-lation holds great promise to be widely adopted in fundamental plant research and crop breeding.

关键词： genome editing short transcriptional enhancers gene upregulation crop breeding

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