A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synth...A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.展开更多
Acetolactate synthase(ALS)-targeting herbicides are among the most widely used weed-control chemicals globally.Mutations in the ALS gene can confer herbicide resistance in crops,thereby allowing selective elimination ...Acetolactate synthase(ALS)-targeting herbicides are among the most widely used weed-control chemicals globally.Mutations in the ALS gene can confer herbicide resistance in crops,thereby allowing selective elimination of weeds without harming crops.Herbicide-resistant ALS alleles were initially discovered in weeds and subsequently developed through artificial mutagenesis techniques.With the advancement of CRISPR/Cas technologies,various genome-editing tools are now available to introduce these resistant alleles,as well as novel variants,into diverse crop species.Moreover,emerging methodologies,such as directed evolution,enable the generation and screening of large populations of random ALS mutants.Consequently,ALS has become one of the most extensively targeted genes in plant gene evolution.This paper provides a comprehensive overview of both conventional and recently developed strategies for ALS evolution,with particular emphasis on CRISPR/Cas-based genome editing and directed evolution.Future perspectives on technological application are also discussed.By advancing our understanding of herbicide-resistant ALS allele development for crop improvement,these methodologies may also pave the way for their application to the evolution of other agronomically important genes.展开更多
Carotenoid cleavage dioxygenase 4(CCD4)controls the rate-limiting step ofβ-ionone biosynthesis,making it a valuable target for healthcare and pharmaceutical applications.Nicotiana tabacum,a carotenoid-richd crop spec...Carotenoid cleavage dioxygenase 4(CCD4)controls the rate-limiting step ofβ-ionone biosynthesis,making it a valuable target for healthcare and pharmaceutical applications.Nicotiana tabacum,a carotenoid-richd crop species,is a promising source forβ-ionone production.This study aimed to modify CCD4 activity to increaseβ-ionone yield in tobacco.We identified two isoforms of CCD4 in N.tabacum,NtCCD4a and NtCCD4b,with NtCCD4a exhibiting significantly higher expression levels than NtCCD4b.Using solid-phase microextraction gas chromatography-mass spectrometry(SPME-GC–MS),we demonstrated that NtCCD4a effectively catalyzes the cleavage ofβ-carotene to produceβ-ionone.To improve its enzymatic activity,we applied structure-based rational design to reconstruct the active pocket of NtCCD4a,followed by high-throughput screening of mutant variants.Three single base mutants,F181G,F184L,and F337M,in NtCCD4a showed enhancedβ-ionone production compared to the wild-type,with F337M yielding the highest amount.No synergistic effects were observed among the three mutants.Transgenic tobacco plants expressing the F181G,F184L,and F337M mutations had acceleratedβ-carotene cleavage and increasedβ-ionone production relative to the wild-type NtCCD4a.Our results establish a framework for the design of CCD4 in major crop species through genome editing technology.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
High-quality silage is the cornerstone to sustainable livestock development and animal food production.As the core fermentation bacteria of silage,Lactobacillus directly regulates silage fermentation by producing lact...High-quality silage is the cornerstone to sustainable livestock development and animal food production.As the core fermentation bacteria of silage,Lactobacillus directly regulates silage fermentation by producing lactic acid,enzymes,and other bioactive molecules.However,traditional screening methods for functional strains are labor-intensive and time-consuming.Recent advances in synthetic biology,particularly the development of CRISPR-Cas genome editing technology,offer a revolutionary approach to designing Lactobacillus strains with customized traits.This review systematically reviewed the importance of silage in sustainable agricultural development and the limitations of current silage preparation and promotion.It also discussed the application of strain engineering approaches in optimizing the phenotypic performance of Lactobacillus for better silage.Building on this,we reviewed the research progress of CRISPR-Cas9 gene editing in Lactobacillus and discussed how to leverage its high efficiency and precision to optimize the strain's traits for improved silage quality and functionality.CRISPR-Cas9 toolkits are expected to achieve directed evolution of strain performance,ultimately yielding next-generation silage microbial inoculants with multiple functions,adaptability to multiple substrates,and eco-friendly characteristics.The use of such innovative biotechnologies would facilitate resource-efficient utilization,promote animal performance and health for sustainable development in livestock production.展开更多
The demand for Erigeron breviscapus,a medicinal Compositae plant with cardiovascular therapeutic properties,has been increasing by 15%annually,exceeding production capacity and necessitating improvements in yield and ...The demand for Erigeron breviscapus,a medicinal Compositae plant with cardiovascular therapeutic properties,has been increasing by 15%annually,exceeding production capacity and necessitating improvements in yield and bioactive compound content.Genetic transformation remains essential for functional genomics,yet current Agrobacterium and biolistic methods are inefficient and expensive.In this study,we cloned the full-length sequences of the BABY BOOM,WUSCHEL and GROWTH-REGULATING FACTOR(GRF)genes of E.breviscapus and then transformed them into E.breviscapus explants.The transformation efficiency for the GRF gene reached 45%,and all the transgenic E.breviscapus plants were fertile without obvious developmental defects.Furthermore,we inserted EbGRF4 and Cas9-EbPDS-sgRNA into the same vector for Agrobacterium-mediated transformation to effectively knock out the PDS gene,resulting in albino seedlings,with a gene editing efficiency of 33.3%.These findings provide a solid foundation for functional genomic research and the genetic improvement of E.breviscapus,as well as an important reference for establishing high-efficiency genetic transformation systems for other medicinal plants.展开更多
OsMAPK6 plays a critical role in regulating rice growth,development,and stress responses.However,the embryonic lethality associated with loss-of-function mutations prevents the generation of homozygous mutant seeds,si...OsMAPK6 plays a critical role in regulating rice growth,development,and stress responses.However,the embryonic lethality associated with loss-of-function mutations prevents the generation of homozygous mutant seeds,significantly hindering functional studies of this gene.Although the weak mutant dsg1 has offered valuable insights into OsMAPK6 function,its extremely low seed-setting rate limits its use for detailed genetic analysis.Here,we employed prime editing to perform precise multi-site modifications at the C-terminus of OsMAPK6,generating a series of osmapk6 mutants with truncated proteins of varying lengths.Among these,the osmapk6(379)and osmapk6(383)mutants exhibited phenotypic defects similar to dsg1,while osmapk6(386)showed a significantly improved seed-setting rate despite persistent developmental defects.Through phenotypic characterization and protein functional analysis,we further clarified how different C-terminal deletion lengths affect plant growth,development,stress responses,and OsMAPK6 protein function.In summary,this study elucidates the importance of the OsMAPK6 C-terminus in rice biology and provides a fertile weak mutant with enhanced seed production,offering a valuable genetic resource for future research on OsMAPK6.展开更多
Background:The golden Syrian hamster is a valuable animal model for studying carcinogenesis,metabolic disorders,cardiovascular diseases,and viral infections due to its biological and pathological similarities to human...Background:The golden Syrian hamster is a valuable animal model for studying carcinogenesis,metabolic disorders,cardiovascular diseases,and viral infections due to its biological and pathological similarities to humans.However,the development of genetically engineered hamsters has lagged behind that of mice and rats,largely because of an embryonic development block at the two-cell stage in vitro.Although CRISPR/Cas9-mediated gene knockout has been achieved in hamsters,precise DNA fragment insertion or conditional knockout(cKO)models have not previously been reported,likely due to technical limitations in embryo manipulation and insufficient efficiency of homology-directed repair(HDR).Methods:In this study,we generated conditional alleles of the ApoF gene in golden Syrian hamsters.A two-cut strategy was applied using Cas9 protein,two sgRNAs,and a single donor plasmid containing exon 2 flanked by loxP sites and two~0.8 kb homology arms.A mixture of Cas9 protein,sgRNAs,and the donor plasmid was microinjected into the pronuclei of one-cell stage hamster embryos.Results:The efficiency of CRISPR/Cas9-mediated loxP knock-in reached up to 27%,and the genetically modified floxed alleles were successfully transmitted through the germline.The functionality of the inserted loxP sites was validated by in vivo Cremediated recombination following local administration of AAV vectors,including AAV-cTnT-Cre in the heart and AAV-CMV-Cre in the brain.Conclusions:To our knowledge,this work represents the first successful establishment of a conditional knockout model in the golden Syrian hamster,providing a valuable tool for mechanistic studies of gene function and disease modeling.展开更多
As we welcome the spring of 2026,we extend our sincere greetings and best wishes to colleagues worldwide in the field of crop science,our partners,and all those committed to sustainable agricultural development!The Ye...As we welcome the spring of 2026,we extend our sincere greetings and best wishes to colleagues worldwide in the field of crop science,our partners,and all those committed to sustainable agricultural development!The Year of the Horse symbolizes endeavor and far-reaching journeys,reflecting our own spirit of continuous exploration and breakthrough innovation on the path of crop science.Here,I extendmysincere appreciation to all our authors and reviewers for their invaluable time,expertise,and dedication,which are instrumental in the success of The Crop Journal,establishing it as a premier platform for the global crop science research community.The Crop Journal publishes its 2026 first issue as a special issue themed“Synthetic Biology for Crop Improvement”,ably vip-edited by four young scientists.The issue provides a comprehensive overview of major advances in the field.In the past few years,crop science has made long strides in metabolic engineering of important pathways in secondary metabolism.The achievements expedite the emergence of synthetic biology as a potent methodology for crop breeding and represent a fundamental paradigm shift from“deciphering crops”to“designing crops”,which is further empowered by artificial intelligence(AI).At this turning point of the New Year,I would like to take this opportunity to provide a brief retrospective and future perspective.展开更多
Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and disea...Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and diseased processes.Owing to their operability and sample accessibility,brain organoids serve as a bridge between in vitro monolayer cell culture models and in vivo animal models.An increasing number of induction protocols for brain organoids have been developed over the preceding decade.A key future research direction will focus on ensuring the complexity and quality of brain organoids.The integration of powerful technologies,such as the CRISP R/Cas9 genome editing and lineage tra cing systems,shall precipitate practical and broad applications of brain organoids.In this review,we discuss the generation and application of brain organoids,as well as their integration with genome editing technologies,in the study of neural development,disease modeling,and mechanistic investigations.The innovative combination of these two technologies may offer a fresh perspective for exploring the fundamental aspects of the human nervous system and related diseases.展开更多
Superconducting diodes,which enable dissipationless supercurrent flow in one direction while blocking it in the reverse direction,are emerging as pivotal components for superconducting electronics.The development of e...Superconducting diodes,which enable dissipationless supercurrent flow in one direction while blocking it in the reverse direction,are emerging as pivotal components for superconducting electronics.The development of editable superconducting diodes could unlock transformative applications,including dynamically reconfigurable quantum circuits that adapt to operational requirements.Here,we report the first observation of the superconducting diode effect(SDE)in LaAlO_(3)/KTaO_(3) heterostructures—a two-dimensional oxide interface superconductor with exceptional tunability.We observe a strong SDE in Hall-bar(or strip-shaped)devices under perpendicular magnetic fields(<15 Oe),with efficiencies above 40%and rectification signals exceeding 10 mV.Through conductive atomic force microscope lithography,we demonstrate reversible nanoscale editing of the SDE’s polarity and efficiency by locally modifying the superconducting channel edges.This approach enables multiple nonvolatile configurations within a single device,realizing an editable superconducting diode.Our work establishes LaAlO_(3)/KTaO_(3) as a platform for vortex-based nonreciprocal transport and provides a pathway toward designer quantum circuits with on-demand functionalities.展开更多
Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).Ho...Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).However,the detection and screening of transgenic lines remain major bottlenecks,being time-consuming,labor-intensive,and inefficient during transformation and subsequent mutation identification.A simple and efficient visual marker system plays a critical role in addressing these challenges.Recent studies demonstrated that the GmW1 and RUBY reporter systems were used to obtain visual transgenic soybean(Glycine max) plants(Chen L et al.2023;Chen et al.2024).展开更多
Genomic disorders affecting the central nervous system(CNS)are among the most complex and devastating conditions in human health.Moreover,these disorders,such as Rett syndrome,spinal muscular atrophy,and Fragile X syn...Genomic disorders affecting the central nervous system(CNS)are among the most complex and devastating conditions in human health.Moreover,these disorders,such as Rett syndrome,spinal muscular atrophy,and Fragile X syndrome,are typically caused by mutations in genes essential for neural development,synaptic function,or cellular homeostasis.Despite the genetic diversity involved,these diseases share key pathological features,including progressive neurodegeneration,disruption of neural circuits,and loss of cognitive or motor function.Meanwhile,one of the significant clinical challenges in treating CNS disorders is the limited regenerative capacity of the adult nervous system,which makes reversing disease progression extremely difficult once symptoms appear.In addition,the blood-brain barrier(BBB)restricts the passage of most systemically administered therapeutics,further complicating effective intervention.Consequently,current treatment options remain largely palliative,and effective cures remain elusive.展开更多
Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neu...Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neurodegenerative fallback.The global prevalence of this disease is estimated at 1 in 770,000(Lee et al.,2023).It is most commonly caused by biallelic(point)mutations in the Wolframin endoplasmic reticulum(ER)transmembrane glycoprotein(WFS1)gene(in case of WS type 1),but mutations in the CDGSH Iron Sulfur Domain 2(CISD2)are also linked to WS(type 2).The latter,however,often present with less severe pathological manifestations(Lee et al.,2023).WFS1 is located on chromosome 4p16.1 and spans over 33 kilobases.Many mutation variants have been identified in WFS1,encompassing missense,nonsense,and frameshift mutations.These mutations are spread across the coding region of WFS1,but certain regions,such as exon 8,the largest exon,appear particularly mutation-prone and associated with the classical WS type 1 phenotype(Lee et al.,2023).展开更多
Base editors are essential tools for precise genome editing in plants.However,achieving high efficiency in C-to-G editing while minimizing byproduct and offtarget mutations remains challenging.In this study,we present...Base editors are essential tools for precise genome editing in plants.However,achieving high efficiency in C-to-G editing while minimizing byproduct and offtarget mutations remains challenging.In this study,we present the development and evaluation of a novel glycosylase-based cytosine base editor(gCBE)for efficient C-to-G editing in rice.Unlike traditional cytosine base editors,which rely on cytosine deamination,gCBE directly excises cytosine to generate an apurinic/apyrimidinic(AP)site,thus circumventing the deamination step and reducing the production of C-to-T byproducts.We constructed several gCBE variants,including N-gCBE,M-gCBE,and C-gCBE,by fusing engineered human UDG2(UNG*)to SpCas9 nickase(nSpCas9,D10A)and tested their editing efficiency and specificity in rice.Our results demonstrate that M-gCBE achieved efficient C-to-G editing(6.3%to 37.5%)similar to OsCGBE(9.4%to 28.1%)at most targets,though with site-dependent variations.Notably,gCBE tools showed a marked reduction in C-to-T byproducts,with average C-to-T mutation rates of 12.5%for N-gCBE and 16.7%for M-gCBE,compared to 53.1%for OsCGBE.Notably,both N-gCBE and M-gCBE were capable of generating homozygous C-to-G mutations in the T_(0)generation,a key advantage over OsCGBE,which predominantly generated C-to-T mutations.Off-target analysis revealed minimal off-target effects with M-gCBE,highlighting its potential for high-precision genome editing.These findings suggest that gCBE tools,particularly M-gCBE,are highly efficient and precise,providing an advanced solution for C-to-G editing in plants and offering promising applications for crop improvement.展开更多
Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional bree...Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional breeding methods raise concerns about reduced genetic diversity,epibreeding propels crop improvement through epigenetic variations that regulate gene expression,ultimately impacting crop yield.Epigenetic regulation in crops encompasses various modes,including histone modification,DNA modification,RNA modification,non-coding RNA,and chromatin remodeling.This review summarizes the epigenetic mechanisms underlying major agronomic traits in maize and identifies candidate epigenetic landmarks in the maize breeding process.We propose a valuable strategy for improving maize yield through epibreeding,combining CRISPR/Cas-based epigenome editing technology and Synthetic Epigenetics(SynEpi).Finally,we discuss the challenges and opportunities associated with maize trait improvement through epibreeding.展开更多
Colorectal cancer(CRC)is the most frequently diagnosed malignancy of the digestive system and the second leading cause of cancer-related deaths worldwide(1).In China,CRC ranks as the second most common cancer with inc...Colorectal cancer(CRC)is the most frequently diagnosed malignancy of the digestive system and the second leading cause of cancer-related deaths worldwide(1).In China,CRC ranks as the second most common cancer with incidence and mortality rates continuing to rise(2).The Chinese Society of Clinical Oncology(CSCO)first introduced its guidelines in 2017,and since then,they have been updated annually to incorporate the latest clinical research findings,drug availability,and expert consensus(3-8).This article presents the key updates in the 2025 edition compared to the 2024 version.展开更多
Bacterial blight(BB),caused by Xanthomonas oryzae pathovar oryzae(Xoo),poses a significant threat to rice production,particularly in Asia and West Africa.Breeding resistance against BB in elite rice varieties is cruci...Bacterial blight(BB),caused by Xanthomonas oryzae pathovar oryzae(Xoo),poses a significant threat to rice production,particularly in Asia and West Africa.Breeding resistance against BB in elite rice varieties is crucial to advancing rice breeding program and supporting smallholder farmers.Transcription Activator-Like effectors(TALes)are key virulence factors in Xoo,with some targeting the susceptibility(S)genes such as the sugar transporter SWEET genes in rice.Among these,SWEET14 is an important S gene,with its promoter bound by the TALe TalC which exists across all sequenced African Xoo isolates.In the present study,we utilized CRISPR/Cas9-based cytidine and adenine base editors to alter the effector binding element(EBE)of TalC in the promoter of SWEET14 in rice cultivars Kitaake,IR24,and Zhonghua 11.Mutations with C to T changes in EBE led to reduced SWEET14 induction by TalC-containing Xoo strains,resulting in resistance to African Xoo isolates reliant on TalC for virulence.Conversely,A to G changes retained SWEET14 inducibility and susceptibility to Xoo in edited lines.Importantly,no off-target mutations were detected at predicted sites,and the edited lines exhibited no obvious defects in major agronomic traits in Kitaake.These results underscore the effectiveness of base editing systems for both molecular biology research and crop improvement endeavors.展开更多
CRISPR-Cas9 has emerged as a powerful tool for gene editing,and it has been widely used in plant functional genomics research and crop genetic breeding(Chen et al.2019).The target specificity of CRISPR-Cas9 relies on ...CRISPR-Cas9 has emerged as a powerful tool for gene editing,and it has been widely used in plant functional genomics research and crop genetic breeding(Chen et al.2019).The target specificity of CRISPR-Cas9 relies on the 20-base-pair single guide RNA(sgRNA),which makes creating plant-specific mutant libraries through large-scale synthesis of sgRNAs targeting multiple genes or even the whole genome relatively quick and straightforward.展开更多
“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 o...“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 1958owing to the name change of the university.展开更多
基金supported by grants from the Guangxi Science and Technology Major Project(GKAA24206023)the Biological Breeding-National Science and Technology Major Project(2024ZD04077)+2 种基金the National Natural Science Foundation of China(32272120)the National Key Research and Development Program of China(2024YFF1000800)the Guangdong Basic Research Center of Excellence for Precise Breeding of Future Crops Major Project(FCBRCE-202502,FCBRCE-202504).
文摘A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.
基金Guangdong Basic and Applied Basic Research Foundation(2023B1515120050,2023A1515110529 and 2024A1515012454)Shenzhen Science and Technology Program(JCYJ20230807145759008 and KJZD20240903100206009).
文摘Acetolactate synthase(ALS)-targeting herbicides are among the most widely used weed-control chemicals globally.Mutations in the ALS gene can confer herbicide resistance in crops,thereby allowing selective elimination of weeds without harming crops.Herbicide-resistant ALS alleles were initially discovered in weeds and subsequently developed through artificial mutagenesis techniques.With the advancement of CRISPR/Cas technologies,various genome-editing tools are now available to introduce these resistant alleles,as well as novel variants,into diverse crop species.Moreover,emerging methodologies,such as directed evolution,enable the generation and screening of large populations of random ALS mutants.Consequently,ALS has become one of the most extensively targeted genes in plant gene evolution.This paper provides a comprehensive overview of both conventional and recently developed strategies for ALS evolution,with particular emphasis on CRISPR/Cas-based genome editing and directed evolution.Future perspectives on technological application are also discussed.By advancing our understanding of herbicide-resistant ALS allele development for crop improvement,these methodologies may also pave the way for their application to the evolution of other agronomically important genes.
基金funded High-Level Talents project of Henan Agricultural University(111-30501301)Project of the National key R&D Program of China(2021YFA0909600)+3 种基金Natural Science Foundation of Henan Province(242300420141)the China Postdoctoral Science Foundation(2020M672308)Cultivation Program for Young Backbone Teachers at Henan University of Technology(DC 11)Science Project 110202101042(JY 19)/2022530000241007,110202102033,110202202038.
文摘Carotenoid cleavage dioxygenase 4(CCD4)controls the rate-limiting step ofβ-ionone biosynthesis,making it a valuable target for healthcare and pharmaceutical applications.Nicotiana tabacum,a carotenoid-richd crop species,is a promising source forβ-ionone production.This study aimed to modify CCD4 activity to increaseβ-ionone yield in tobacco.We identified two isoforms of CCD4 in N.tabacum,NtCCD4a and NtCCD4b,with NtCCD4a exhibiting significantly higher expression levels than NtCCD4b.Using solid-phase microextraction gas chromatography-mass spectrometry(SPME-GC–MS),we demonstrated that NtCCD4a effectively catalyzes the cleavage ofβ-carotene to produceβ-ionone.To improve its enzymatic activity,we applied structure-based rational design to reconstruct the active pocket of NtCCD4a,followed by high-throughput screening of mutant variants.Three single base mutants,F181G,F184L,and F337M,in NtCCD4a showed enhancedβ-ionone production compared to the wild-type,with F337M yielding the highest amount.No synergistic effects were observed among the three mutants.Transgenic tobacco plants expressing the F181G,F184L,and F337M mutations had acceleratedβ-carotene cleavage and increasedβ-ionone production relative to the wild-type NtCCD4a.Our results establish a framework for the design of CCD4 in major crop species through genome editing technology.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
基金supported by the National Nature Science Foundation of China(No.U20A2002)。
文摘High-quality silage is the cornerstone to sustainable livestock development and animal food production.As the core fermentation bacteria of silage,Lactobacillus directly regulates silage fermentation by producing lactic acid,enzymes,and other bioactive molecules.However,traditional screening methods for functional strains are labor-intensive and time-consuming.Recent advances in synthetic biology,particularly the development of CRISPR-Cas genome editing technology,offer a revolutionary approach to designing Lactobacillus strains with customized traits.This review systematically reviewed the importance of silage in sustainable agricultural development and the limitations of current silage preparation and promotion.It also discussed the application of strain engineering approaches in optimizing the phenotypic performance of Lactobacillus for better silage.Building on this,we reviewed the research progress of CRISPR-Cas9 gene editing in Lactobacillus and discussed how to leverage its high efficiency and precision to optimize the strain's traits for improved silage quality and functionality.CRISPR-Cas9 toolkits are expected to achieve directed evolution of strain performance,ultimately yielding next-generation silage microbial inoculants with multiple functions,adaptability to multiple substrates,and eco-friendly characteristics.The use of such innovative biotechnologies would facilitate resource-efficient utilization,promote animal performance and health for sustainable development in livestock production.
基金supported by the National Natural Science Foundation of China(82160727)the Major Science and Technique Programs in Yunnan Province(202304BT090021-ML05)Yunnan Agricultural University research start-up Fund(KY2022-02).
文摘The demand for Erigeron breviscapus,a medicinal Compositae plant with cardiovascular therapeutic properties,has been increasing by 15%annually,exceeding production capacity and necessitating improvements in yield and bioactive compound content.Genetic transformation remains essential for functional genomics,yet current Agrobacterium and biolistic methods are inefficient and expensive.In this study,we cloned the full-length sequences of the BABY BOOM,WUSCHEL and GROWTH-REGULATING FACTOR(GRF)genes of E.breviscapus and then transformed them into E.breviscapus explants.The transformation efficiency for the GRF gene reached 45%,and all the transgenic E.breviscapus plants were fertile without obvious developmental defects.Furthermore,we inserted EbGRF4 and Cas9-EbPDS-sgRNA into the same vector for Agrobacterium-mediated transformation to effectively knock out the PDS gene,resulting in albino seedlings,with a gene editing efficiency of 33.3%.These findings provide a solid foundation for functional genomic research and the genetic improvement of E.breviscapus,as well as an important reference for establishing high-efficiency genetic transformation systems for other medicinal plants.
基金supported by the National Natural Science Foundation of China(Grant Nos.32441024,32572315,and U25A20674)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2021229)+1 种基金the Heilongjiang Key Research and Development Program,China(Grant No.2025ZX04B02)the Young Scientist Group Project of Northeast Institute of Geography and Agroecology,Chinese Academy of Sciences(Grant No.2023QNXZ02).
文摘OsMAPK6 plays a critical role in regulating rice growth,development,and stress responses.However,the embryonic lethality associated with loss-of-function mutations prevents the generation of homozygous mutant seeds,significantly hindering functional studies of this gene.Although the weak mutant dsg1 has offered valuable insights into OsMAPK6 function,its extremely low seed-setting rate limits its use for detailed genetic analysis.Here,we employed prime editing to perform precise multi-site modifications at the C-terminus of OsMAPK6,generating a series of osmapk6 mutants with truncated proteins of varying lengths.Among these,the osmapk6(379)and osmapk6(383)mutants exhibited phenotypic defects similar to dsg1,while osmapk6(386)showed a significantly improved seed-setting rate despite persistent developmental defects.Through phenotypic characterization and protein functional analysis,we further clarified how different C-terminal deletion lengths affect plant growth,development,stress responses,and OsMAPK6 protein function.In summary,this study elucidates the importance of the OsMAPK6 C-terminus in rice biology and provides a fertile weak mutant with enhanced seed production,offering a valuable genetic resource for future research on OsMAPK6.
基金State Key Laboratory Special Fund,Grant/Award Number:2060204Open Research Project in State Key Laboratory of Vascular Homeostasis and Remodeling,Grant/Award Number:Peking University,202411+3 种基金The Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01Haihe Laboratory of Cell Ecosystem Innovation Fund,Grant/Award Number:HH24KYZX0007CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-024,2022-I2M-1-020 and 2023-I2M-2-001the National Key Research and Development Program of China from the Ministry of Science and Technology,Grant/Award Number:2021YFF0702802。
文摘Background:The golden Syrian hamster is a valuable animal model for studying carcinogenesis,metabolic disorders,cardiovascular diseases,and viral infections due to its biological and pathological similarities to humans.However,the development of genetically engineered hamsters has lagged behind that of mice and rats,largely because of an embryonic development block at the two-cell stage in vitro.Although CRISPR/Cas9-mediated gene knockout has been achieved in hamsters,precise DNA fragment insertion or conditional knockout(cKO)models have not previously been reported,likely due to technical limitations in embryo manipulation and insufficient efficiency of homology-directed repair(HDR).Methods:In this study,we generated conditional alleles of the ApoF gene in golden Syrian hamsters.A two-cut strategy was applied using Cas9 protein,two sgRNAs,and a single donor plasmid containing exon 2 flanked by loxP sites and two~0.8 kb homology arms.A mixture of Cas9 protein,sgRNAs,and the donor plasmid was microinjected into the pronuclei of one-cell stage hamster embryos.Results:The efficiency of CRISPR/Cas9-mediated loxP knock-in reached up to 27%,and the genetically modified floxed alleles were successfully transmitted through the germline.The functionality of the inserted loxP sites was validated by in vivo Cremediated recombination following local administration of AAV vectors,including AAV-cTnT-Cre in the heart and AAV-CMV-Cre in the brain.Conclusions:To our knowledge,this work represents the first successful establishment of a conditional knockout model in the golden Syrian hamster,providing a valuable tool for mechanistic studies of gene function and disease modeling.
文摘As we welcome the spring of 2026,we extend our sincere greetings and best wishes to colleagues worldwide in the field of crop science,our partners,and all those committed to sustainable agricultural development!The Year of the Horse symbolizes endeavor and far-reaching journeys,reflecting our own spirit of continuous exploration and breakthrough innovation on the path of crop science.Here,I extendmysincere appreciation to all our authors and reviewers for their invaluable time,expertise,and dedication,which are instrumental in the success of The Crop Journal,establishing it as a premier platform for the global crop science research community.The Crop Journal publishes its 2026 first issue as a special issue themed“Synthetic Biology for Crop Improvement”,ably vip-edited by four young scientists.The issue provides a comprehensive overview of major advances in the field.In the past few years,crop science has made long strides in metabolic engineering of important pathways in secondary metabolism.The achievements expedite the emergence of synthetic biology as a potent methodology for crop breeding and represent a fundamental paradigm shift from“deciphering crops”to“designing crops”,which is further empowered by artificial intelligence(AI).At this turning point of the New Year,I would like to take this opportunity to provide a brief retrospective and future perspective.
基金Special Projectfor Clinical Research of Shanghai Municipal Health Commission,No.202140403Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai,No.PWZxq2022-05+2 种基金Natural Science Foundation of Ningxia Hui Autonomous Region,No.2024AAC05084Ningxia Hui Autonomous Region Key Research and Development Program,No.2021BEG03084National Natural Science Foundation of China,Nos.32370895,32070862。
文摘Brain organoids are artificial neural tissues derived in vitro,containing a variety of cell types,as well as structural and/or functional brain regions.They can partially mimic brain physiological activities and diseased processes.Owing to their operability and sample accessibility,brain organoids serve as a bridge between in vitro monolayer cell culture models and in vivo animal models.An increasing number of induction protocols for brain organoids have been developed over the preceding decade.A key future research direction will focus on ensuring the complexity and quality of brain organoids.The integration of powerful technologies,such as the CRISP R/Cas9 genome editing and lineage tra cing systems,shall precipitate practical and broad applications of brain organoids.In this review,we discuss the generation and application of brain organoids,as well as their integration with genome editing technologies,in the study of neural development,disease modeling,and mechanistic investigations.The innovative combination of these two technologies may offer a fresh perspective for exploring the fundamental aspects of the human nervous system and related diseases.
基金supported by the National Key R&D Program of China (Grant No.2023YFA1406400)the National Natural Science Foundation of China (Grant Nos.12534005 and 12325402)。
文摘Superconducting diodes,which enable dissipationless supercurrent flow in one direction while blocking it in the reverse direction,are emerging as pivotal components for superconducting electronics.The development of editable superconducting diodes could unlock transformative applications,including dynamically reconfigurable quantum circuits that adapt to operational requirements.Here,we report the first observation of the superconducting diode effect(SDE)in LaAlO_(3)/KTaO_(3) heterostructures—a two-dimensional oxide interface superconductor with exceptional tunability.We observe a strong SDE in Hall-bar(or strip-shaped)devices under perpendicular magnetic fields(<15 Oe),with efficiencies above 40%and rectification signals exceeding 10 mV.Through conductive atomic force microscope lithography,we demonstrate reversible nanoscale editing of the SDE’s polarity and efficiency by locally modifying the superconducting channel edges.This approach enables multiple nonvolatile configurations within a single device,realizing an editable superconducting diode.Our work establishes LaAlO_(3)/KTaO_(3) as a platform for vortex-based nonreciprocal transport and provides a pathway toward designer quantum circuits with on-demand functionalities.
基金supported by the Jilin Science and Technology Development Program,China (20240602032RC)the Jilin Agricultural Science and Technology Innovation Project,China (CXGC2024ZD001)+1 种基金the Jilin Agricultural Science and Technology Innovation Project,China (CXGC2024ZY012)the Jilin Province Development and Reform Commission-Project for Improving the Independent Innovation Capacity of Major Grain Crops,China (2024C002)。
文摘Emerging and powerful genome editing tools,particularly CRISPR/Cas9,are facilitating functional genomics research and accelerating crop improvement(Jiang et al.2021;Cao et al.2023;Chen C et al.2023;Liu et al.2023a).However,the detection and screening of transgenic lines remain major bottlenecks,being time-consuming,labor-intensive,and inefficient during transformation and subsequent mutation identification.A simple and efficient visual marker system plays a critical role in addressing these challenges.Recent studies demonstrated that the GmW1 and RUBY reporter systems were used to obtain visual transgenic soybean(Glycine max) plants(Chen L et al.2023;Chen et al.2024).
基金the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(RS-2024-00344633)HYC acknowledges the financial support from the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(RS-2023-00211360)Biomaterials Specialized Graduate Program through the Korea Environmental Industry&Technology Institute(KEITI)funded by the Ministry of Environment(MOE).
文摘Genomic disorders affecting the central nervous system(CNS)are among the most complex and devastating conditions in human health.Moreover,these disorders,such as Rett syndrome,spinal muscular atrophy,and Fragile X syndrome,are typically caused by mutations in genes essential for neural development,synaptic function,or cellular homeostasis.Despite the genetic diversity involved,these diseases share key pathological features,including progressive neurodegeneration,disruption of neural circuits,and loss of cognitive or motor function.Meanwhile,one of the significant clinical challenges in treating CNS disorders is the limited regenerative capacity of the adult nervous system,which makes reversing disease progression extremely difficult once symptoms appear.In addition,the blood-brain barrier(BBB)restricts the passage of most systemically administered therapeutics,further complicating effective intervention.Consequently,current treatment options remain largely palliative,and effective cures remain elusive.
基金Research into Wolfram syndrome in the De Groef team has been supported by the Eye Hope Foundation(Belgium),Wolfram UK(UK)and The Snow Foundation(USA).
文摘Wolfram syndrome(WS)is a rare autosomal rece s s i ve disease characte r i zed by the development of diabetes insipidus,diabetes mellitus,optic atrophy,and deafness(often referred to as DIDMOAD),and overall severe neurodegenerative fallback.The global prevalence of this disease is estimated at 1 in 770,000(Lee et al.,2023).It is most commonly caused by biallelic(point)mutations in the Wolframin endoplasmic reticulum(ER)transmembrane glycoprotein(WFS1)gene(in case of WS type 1),but mutations in the CDGSH Iron Sulfur Domain 2(CISD2)are also linked to WS(type 2).The latter,however,often present with less severe pathological manifestations(Lee et al.,2023).WFS1 is located on chromosome 4p16.1 and spans over 33 kilobases.Many mutation variants have been identified in WFS1,encompassing missense,nonsense,and frameshift mutations.These mutations are spread across the coding region of WFS1,but certain regions,such as exon 8,the largest exon,appear particularly mutation-prone and associated with the classical WS type 1 phenotype(Lee et al.,2023).
基金supported by the National Natural Science Foundation of China(82404798)the Natural Science Foundation of Sichuan Province(2024NSFSC1831)+1 种基金the National Key Laboratory for Tropical Crop Breeding(NKLTCB-RC202403,NKLTCBZRJJ4)the Hainan Seed Industrial Laboratory(B22C1000P).
文摘Base editors are essential tools for precise genome editing in plants.However,achieving high efficiency in C-to-G editing while minimizing byproduct and offtarget mutations remains challenging.In this study,we present the development and evaluation of a novel glycosylase-based cytosine base editor(gCBE)for efficient C-to-G editing in rice.Unlike traditional cytosine base editors,which rely on cytosine deamination,gCBE directly excises cytosine to generate an apurinic/apyrimidinic(AP)site,thus circumventing the deamination step and reducing the production of C-to-T byproducts.We constructed several gCBE variants,including N-gCBE,M-gCBE,and C-gCBE,by fusing engineered human UDG2(UNG*)to SpCas9 nickase(nSpCas9,D10A)and tested their editing efficiency and specificity in rice.Our results demonstrate that M-gCBE achieved efficient C-to-G editing(6.3%to 37.5%)similar to OsCGBE(9.4%to 28.1%)at most targets,though with site-dependent variations.Notably,gCBE tools showed a marked reduction in C-to-T byproducts,with average C-to-T mutation rates of 12.5%for N-gCBE and 16.7%for M-gCBE,compared to 53.1%for OsCGBE.Notably,both N-gCBE and M-gCBE were capable of generating homozygous C-to-G mutations in the T_(0)generation,a key advantage over OsCGBE,which predominantly generated C-to-T mutations.Off-target analysis revealed minimal off-target effects with M-gCBE,highlighting its potential for high-precision genome editing.These findings suggest that gCBE tools,particularly M-gCBE,are highly efficient and precise,providing an advanced solution for C-to-G editing in plants and offering promising applications for crop improvement.
基金supported by funding from the National Key R&D Program of China(2023ZD0407304)the Sci-Tech Innovation 2030 Agenda(2022ZD0115703)Fundamental Research Funds for Central Non-Profit of Chinese Academy of Agricultural Sciences(Y2023PT20).
文摘Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional breeding methods raise concerns about reduced genetic diversity,epibreeding propels crop improvement through epigenetic variations that regulate gene expression,ultimately impacting crop yield.Epigenetic regulation in crops encompasses various modes,including histone modification,DNA modification,RNA modification,non-coding RNA,and chromatin remodeling.This review summarizes the epigenetic mechanisms underlying major agronomic traits in maize and identifies candidate epigenetic landmarks in the maize breeding process.We propose a valuable strategy for improving maize yield through epibreeding,combining CRISPR/Cas-based epigenome editing technology and Synthetic Epigenetics(SynEpi).Finally,we discuss the challenges and opportunities associated with maize trait improvement through epibreeding.
基金supported by the National Natural Science Foundation of China(No.82373415)Beijing Xisike Clinical Oncology Research Foundation(No.Ytongshu2021/ms-0003)。
文摘Colorectal cancer(CRC)is the most frequently diagnosed malignancy of the digestive system and the second leading cause of cancer-related deaths worldwide(1).In China,CRC ranks as the second most common cancer with incidence and mortality rates continuing to rise(2).The Chinese Society of Clinical Oncology(CSCO)first introduced its guidelines in 2017,and since then,they have been updated annually to incorporate the latest clinical research findings,drug availability,and expert consensus(3-8).This article presents the key updates in the 2025 edition compared to the 2024 version.
基金supported by a sub-award to the University of Missouri from the Heinrich Heine University of Dusseldorf funded by the Bill&Melinda Gates Foundation(OPP1155704)(Bing Yang)and the China Scholar Council(Chenhao Li,as a joint Ph.D.student).
文摘Bacterial blight(BB),caused by Xanthomonas oryzae pathovar oryzae(Xoo),poses a significant threat to rice production,particularly in Asia and West Africa.Breeding resistance against BB in elite rice varieties is crucial to advancing rice breeding program and supporting smallholder farmers.Transcription Activator-Like effectors(TALes)are key virulence factors in Xoo,with some targeting the susceptibility(S)genes such as the sugar transporter SWEET genes in rice.Among these,SWEET14 is an important S gene,with its promoter bound by the TALe TalC which exists across all sequenced African Xoo isolates.In the present study,we utilized CRISPR/Cas9-based cytidine and adenine base editors to alter the effector binding element(EBE)of TalC in the promoter of SWEET14 in rice cultivars Kitaake,IR24,and Zhonghua 11.Mutations with C to T changes in EBE led to reduced SWEET14 induction by TalC-containing Xoo strains,resulting in resistance to African Xoo isolates reliant on TalC for virulence.Conversely,A to G changes retained SWEET14 inducibility and susceptibility to Xoo in edited lines.Importantly,no off-target mutations were detected at predicted sites,and the edited lines exhibited no obvious defects in major agronomic traits in Kitaake.These results underscore the effectiveness of base editing systems for both molecular biology research and crop improvement endeavors.
基金supported by the National Natural Science Foundation of China(32272670 and 31972986)the Key Research and Development Program of Shaanxi Province,China(2023-YBNY-059)。
文摘CRISPR-Cas9 has emerged as a powerful tool for gene editing,and it has been widely used in plant functional genomics research and crop genetic breeding(Chen et al.2019).The target specificity of CRISPR-Cas9 relies on the 20-base-pair single guide RNA(sgRNA),which makes creating plant-specific mutant libraries through large-scale synthesis of sgRNAs targeting multiple genes or even the whole genome relatively quick and straightforward.
文摘“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 1958owing to the name change of the university.
