Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Germline Gene-Editing Creates Enhanced Livestock-Technical and Especially Ethical Issues Challenge Its Use in Humans

Using clustered regularly interspaced short palindromic repeats(CRISPR)-based molecular tools,scientists are engineering-as they are also doing with plants.-animals with advantageous traits,like disease resistance and improved food yield.While these innovative techniques could one day be applied in humans,technical hurdles and ethical concerns likely place this possibility far in the future,The enhancements rely on germline gene editing,which alters the genes in a way that passes the changes on to offspring.Ger m-line gene editing differs from the somatic cell gene editing used in the highly promising new treatment recently approved for the human disease sickle cell anemia.

Elite,transformable haploid inducers in maize

The introduction of alleles into commercial crop breeding pipelines is both time consuming and costly.Two technologies that are disrupting traditional breeding processes are doubled haploid(DH)breeding and genome editing(GE).Recently,these techniques were combined into a GE trait delivery system called HI-Edit(Haploid Inducer-Edit).In HI-Edit,the pollen of a haploid inducer line is reprogrammed to deliver GE traits to any variety,obviating recurrent selection.For HI-Edit to operate at scale,an efficient transformable HI line is needed,but most maize varieties are recalcitrant to transformation,and haploid inducers are especially difficult to transform given their aberrant reproductive behaviors.Leveraging marker assisted selection and a three-tiered testing scheme,we report the development of new Iodent and Stiff Stalk maize germplasm that are transformable,have high haploid induction rates,and exhibit a robust,genetically-dominant anthocyanin native trait that may be used for rapid haploid identification.We show that transformation of these elite‘‘HI-Edit”lines is enhanced using the BABYBOOM and WUSCHEL morphogenetic factors.Finally,we evaluate the HI-Edit performance of one of the lines against both Stiff Stalk and non-Stiff Stalk testers.The strategy and results of this study should facilitate the development of commercially scalable HI-Edit systems in diverse crops.

Enemies atpeace:Recentprogressin Agrobacterium-mediated cereal transformation

Agrobacterium tumefaciens mediated plant transformation is a versatile tool for plant genetic engineering following its discovery nearly half a century ago.Numerous modifications were made in its application to increase efficiency,especially in the recalcitrant major cereals plants.Recent breakthroughs in transformation efficiency continue its role as a mainstream technique in CRISPR/Cas-based genome editing and gene stacking.These modifications led to higher transformation frequency and lower but more stable transgene copies with the capability to revolutionize modern agriculture.In this review,we provide a brief overview of the history of Agrobacterium-mediated plant transformation and focus on the most recent progress to improve the system in both the Agrobacterium and the host recipient.A promising future for transformation in biotechnology and agriculture is predicted.

Brief Introduction to“Journal of Jilin University(Science Edition)”

“Journal of Jilin University(Science Edition)”is a comprehensive academic journal in the fields of science sponsored by Jilin University and administrated by the Ministry of Education of the People's Republic of China.The journal started publication in 1955.The original name at starting publication was“Journal of Natural Science of Northeast People University”.

Brief Introduction to “Journal of Jilin University (Science Edition)”

“Journal of Jilin University(Science Edition)” is a comprehensive academic journal in the fields of science sponsored by Jilin University and administrated by the Ministry of Education of the People’s Republic of China.The journal started publication in 1955.The original name at starting publication was “Journal of Natural Science of Northeast People University”.

Brief Introduction to “Journal of Jilin University(Science Edition)”

“Journal of Jilin University(Science Edition)” is a comprehensive academic journal in the fields of science sponsored by Jilin University and administrated by the Ministry of Education of the People’s Republic of China.The journal started publication in 1955.The original name at starting publication was “Journal of Natural Science of Northeast People University”,which was changed into “Acta Scientiarum Naturalium Universitatis Jilinensis” in 1958 owing to the name change of the university.

A simple and efficient CRISPR/Cas9 system permits ultra-multiplex genome editing in plants

The development and maturation of the CRISPR/Cas genome editing system provides a valuable tool for plant functional genomics and genetic improvement.Currently available genome-editing tools have a limited number of targets,restricting their application in genetic research.In this study,we developed a novel CRISPR/Cas9 plant ultra-multiplex genome editing system consisting of two template vectors,eight donor vectors,four destination vectors,and one primer-design software package.By combining the advantages of Golden Gate cloning to assemble multiple repetitive fragments and Gateway recombination to assemble large fragments and by changing the structure of the amplicons used to assemble sg RNA expression cassettes,the plant ultra-multiplex genome editing system can assemble a single binary vector targeting more than 40 genomic loci.A rice knockout vector containing 49 sg RNA expression cassettes was assembled and a high co-editing efficiency was observed.This plant ultra-multiplex genome editing system advances synthetic biology and plant genetic engineering.

The concept of gene therapy for glaucoma:the dream that has not come true yet

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in glaucoma.Since glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent manner.The most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic profile.The gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve crush-model.Reported gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

引导编辑技术的研究进展及应用

以CRISPR/Cas9为基础的引导编辑系统是新开发出的一种基因编辑技术,可以精确实现12种碱基的互换、插入和缺失,并且不需要产生双链断裂和引入外源供体DNA。本文从基因编辑的发展、引导编辑系统的原理、特点、优化、脱靶效应、在动植物和基因治疗研究中的应用、引导编辑系统的设计等几方面进行综述,为促进相关领域的科研工作者了解引导编辑系统及进一步利用引导编辑系统在动植物科学基础研究和育种方面的应用提供指导。

Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity

Genetic information is transcribed from genomic DNA to mRNA,which is then translated into threedimensional proteins.mRNAs can undergo various post-transcriptional modifications,including RNA editing that alters mRNA sequences,ultimately affecting protein function.In this study,RNA editing was identified at the 499th base(c.499)of human vaccinia-related kinase 2(VRK2).This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine(with adenine base)to valine(with guanine base).Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2,which leads to an increase in tumor cell proliferation.Earlier we reported that VRK2 directly interacts with dystrobrevin-binding protein(dysbindin)and results in reducing its stability.Herein,we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valinecontaining VRK2.Dysbindin interacts with cyclin D and thereby regulates its expression and function.The reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression,resulting in increased tumor growth and reduction in survival rates.It has also been observed that in patient samples,VRK2 level was elevated in breast cancer tissue compared to normal breast tissue.Additionally,the isoleucine form of VRK2 exhibited a greater increase in breast cancer tissue.Therefore,it is concluded that VRK2,especially dependent on the 167th variant amino acid,can be one of the indexes of tumor progression and proliferation.

Journal of Northeast Agricultural University(English Edition) Instruction to Authors

Aims and Scope Journal of Northeast Agricultural University(English Edition) is a comprehensive academic journal on agricultural sciences sponsored by Northeast Agricultural University and distributed worldwide. It is a peer reviewed journal published quarterly and mainly publishes review and research articles that reflect the latest achievements on crop science, horticulture, plant protection, resource and environment, animal science, veterinary medicine, agricultural engineering and technology, agricultural water conservancy, life science, biotechnology and food science.

Distribution Line Longitudinal ProtectionMethod Based on Virtual Measurement Current Restraint

As an effective approach to achieve the“dual-carbon”goal,the grid-connected capacity of renewable energy increases constantly.Photovoltaics are the most widely used renewable energy sources and have been applied on various occasions.However,the inherent randomness,intermittency,and weak support of grid-connected equipment not only cause changes in the original flow characteristics of the grid but also result in complex fault characteristics.Traditional overcurrent and differential protection methods cannot respond accurately due to the effects of unknown renewable energy sources.Therefore,a longitudinal protection method based on virtual measurement of current restraint is proposed in this paper.The positive sequence current data and the network parameters are used to calculate the virtual measurement current which compensates for the output current of photovoltaic(PV).The waveform difference between the virtual measured current and the terminal current for internal and external faults is used to construct the protection method.An improved edit distance algorithm is proposed to measure the similarity between virtual measurement current and terminal measurement current.Finally,the feasibility of the protection method is verified through PSCAD simulation.

New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

Problems of Music Interpretation and Its Expression: On the Example of the Violin

Music is essentially a sonic phenomenon, an intangible art that we experience through our auditory organs. It is written as a physical note on paper. It is the result of harmony and composition of music that expresses the meaning of music created from the author’s mind, thinking, skills, and feelings, or composition or work. If a composition is not interpreted by a musician and set to music, it is nothing more than a notation and notation written down on paper. The main process of conveying the composition to the listeners through the musician’s interpretation of the music is somewhat overlooked. Therefore, in this research, the musician’s thinking and editing method, and how to express it through interpretation, were the doctoral dissertation and articles of researchers such as have been studied in comparison.

SNAPSHOTS OF NOTABLE BOOKS ON AFRICA

Ubuntu Edited by PAUL NNODIM&AUSTIN OKIGBO Leuven University Press Ubuntu,an African philosophical tradition,embodies the capacity for one human to empathise with another,encapsulating African humanism,communalism,and belonging.The late Archbishop Desmond Tutu foresaw its resonance with the moral sensibilities of black South Africans in the 1990s,making it the foundational ethical framework for navigating a new era of reconciliation and forgiveness post-apartheid,amidst a backdrop of historical racial violence.

THOUGHTS FOR A NEW ERA

China celebrates its National Security Education Day on 15 April.This year marks the 10th anniversary of the holistic approach to national security put forward by Chinese President Xi Jinping.Guided by the approach,China has navigated drastic changes in the international landscape and kept itself well positioned in the pursuit of development and security.Xi has reiterated the importance of national security on many occasions.Edited excerpts of his speeches on this topic since 2016 follow.

加大功率 更易搭配 Naim Uniti Nova Power Edition一体化播放器

Uniti系列自推出以来,一直都是英国Naim的当家产品。特别是在2016年推出全新的Uniti后,更是深受市场的欢迎,以极具科技感和时尚气息的外观,丰富的功能以及便捷的使用体验,俘虏了不少用家的心。2024年,Uniti系列再添新品,在原有UnitiNova的基础上,推出了功率增强版Uniti NovaPowerEdition。究竟这款全新升级版旗舰级一体化播放器有何特别之处?我们一起一探究竟!

Agrobacterium tumefaciens-mediated transformation of embryogenic callus and CRISPR/Cas9-mediated genome editing in‘Feizixiao'litchi

Litchi(Litchi chinensis Sonn.)is a type of commercially prevalent subtropical and tropical fruit.Since litchi has a highly heterozygous genetic background and a long reproductive cycle,conventional breeding methods(such as hybridization)have limited ability to nurture new litchi cultivars.Here,an efficient and stable Agrobacterium tumefaciens-mediated genetic transformation of embryogenic callus was established in‘Feizixiao’litchi.Transgenic materials were verified using polymerase chain reaction(PCR)analysis,β-glucuronidase(GUS)assay,and green fluorescent protein(GFP)assay.To implement the technology of the Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)/associated protein 9(CRISPR/Cas9)technology in‘Feizixiao’litchi and verify the validity of these transformation systems,the litchi polyphenol oxidase gene(LcPPO,JF926153)was knocked out.Various categories of mutations,covering base insertions,deletions,and substitutions,were found in transgenic materials via sequence analysis.The transformation system achieved high feasibility and efficiency,and the system of CRISPR/Cas9 was successfully employed to edit genes in‘Feizixiao’litchi.This work provides an essential foundation for investigating the functions of genes and accelerating litchi genetic improvement.