Development of Machine Learning Methods for Accurate Prediction of Plant Disease Resistance

The traditional method of screening plants for disease resistance phenotype is both time-consuming and costly.Genomic selection offers a potential solution to improve efficiency,but accurately predicting plant disease resistance remains a challenge.In this study,we evaluated eight different machine learning(ML)methods,including random forest classification(RFC),support vector classifier(SVC),light gradient boosting machine(lightGBM),random forest classification plus kinship(RFC_K),support vector classification plus kinship(SVC_K),light gradient boosting machine plus kinship(lightGBM_K),deep neural network genomic prediction(DNNGP),and densely connected convolutional networks(DenseNet),for predicting plant disease resistance.Our results demonstrate that the three plus kinship(K)methods developed in this study achieved high prediction accuracy.Specifically,these methods achieved accuracies of up to 95%for rice blast(RB),85%for rice black-streaked dwarf virus(RBSDV),and 85%for rice sheath blight(RSB)when trained and applied to the rice diversity panel I(RDPI).Furthermore,the plus K models performed well in predicting wheat blast(WB)and wheat stripe rust(WSR)diseases,with mean accuracies of up to 90%and 93%,respectively.To assess the generalizability of our models,we applied the trained plus K methods to predict RB disease resistance in an independent population,rice diversity panel II(RDPII).Concurrently,we evaluated the RB resistance of RDPII cultivars using spray inoculation.Comparing the predictions with the spray inoculation results,we found that the accuracy of the plus K methods reached 91%.These findings highlight the effectiveness of the plus K methods(RFC_K,SVC_K,and lightGBM_K)in accurately predicting plant disease resistance for RB,RBSDV,RSB,WB,and WSR.The methods developed in this study not only provide valuable strategies for predicting disease resistance,but also pave the way for using machine learning to streamline genome-based crop breeding.

Ubiquitination-mediated protein degradation and modification:an emerging theme in plant-microbe interactions

Post-translational modification is central to protein stability and to the modulation of protein activity. Various types of protein modification, such as phosphorylation, methylation, acetylation, myristoylation, glycosylation, and ubiquitination, have been reported. Among them, ubiquitination distinguishes itself from others in that most of the ubiquitinated proteins are targeted to the 26S proteasome for degradation. The ubiquitin/26S proteasome system constitutes the major protein degradation pathway in the cell. In recent years, the importance of the ubiquitination machinery in the control of numerous eukaryotic cellular functions has been increasingly appreciated. Increasing number of E3 ubiquitin ligases and their substrates, including a variety of essential cellular regulators have been identified. Studies in the past several years have revealed that the ubiquitination system is important for a broad range of plant developmental processes and responses to abiotic and biotic stresses. This review discusses recent advances in the functional analysis of ubiquitination-associated proteins from plants and pathogens that play important roles in plant-microbe interactions.

Hepatocellular carcinoma and macrophage interaction induced tumor immunosuppressionvia Treg requires TLR4 signaling

AIM: To investigated the interaction between toll-like receptor 4 (TLR4)-activated hepatoma cells and macrophages in the induction of tumor-immune suppression mediated by CD4+CD25high family of transcription factor P3 (FOXP3) regulatory T cells (Tregs). METHODS: The proportion of FOXP3+ Tregs was identified in peripheral blood and tumor tissues of 60 hepatocellular carcinoma (HCC) patients. TLR4 expression was examined in tumor tissues and cell lines. The correlation was examined between FOXP3+ Tregs in peripheral blood and TLR4 expression of HCC tissues. Following activation of TLR4 in H22 murine hepatoma cells pre-incubated with lipopolysaccharide (LPS) and co-cultured with macrophage cell line RAW246.7, the synthesis of cytokines tumor necrosis factor-α, CCL22, and interleukin (IL)-10 by the two cell lines was detected and analyzed. RESULTS: FOXP3+ Tregs were enriched in tumor sites, and circulating FOXP3+ Tregs were increased in HCC patients in correlation with multiple tumor foci and up-regulated TLR4 expression in HCC tissues. Semi-quantitative analysis indicated that TLR4 was over-expressed in HCC compared with the matched normal tissues. Cell cultivation experiments indicated that the mRNAs of IL-10 and CCL22 were significantly up-regulated in the RAW246.7 cell line when co-cultured with LPS preincubated H22 cells. CONCLUSION: In hepatoma cell lines, TLR4 may indirectly facilitate the recruitment of Tregs to the tumor site and promote intrahepatic metastasis through its interaction with macrophages.

Rapid Detection of Wheat Blast Pathogen Magnaporthe oryzae Triticum Pathotype Using Genome-Specific Primers and Cas12a-mediated Technology

Wheat blast,caused by the fungus Magnaporthe oryzae Triticum(MoT)pathotype,is a devastating disease persistent in South America and Bangladesh.Since MoT generally fails to cause visual symptoms in wheat until the heading stage when the infection would have advanced,disease control by fungicide application solely based on the detection of visual symptoms is ineffective.To develop an accurate and sensitive method to detect MoT at the seedling and vegetative stages for disease control,we sequenced the genomes of two MoT isolates from Brazil and identified two DNA fragments,MoT-6098 and MoT-6099,that are present in the MoT genome but not in the genome of the rice-infecting Magnaporthe oryzae Oryzae(MoO)pathotype.Using polymerase chain reaction(PCR),we confirmed the specificity of the two markers in 53 MoT and MoO isolates from South America and Bangladesh.To test the efficiency of the two markers,we first established a loop-mediated isothermal amplification(LAMP)method to detect MoT at isothermal conditions,without the use of a PCR machine.Following this,we used the Cas12a protein and guide RNAs(gRNAs)to target the MoT-6098 and MoT-6099 sequences.The activated Cas12a showed indiscriminate single-stranded deoxyribonuclease(ssDNase)activity.We then combined targetdependent Cas12a ssDNase activation with recombinase polymerase amplification(RPA)and nucleic acid lateral flow immunoassay(NALFIA)to develop a method that accurately,sensitively,and cost-effectively detects MoT-specific DNA sequences in infected wheat plants.This novel technique can be easily adapted for the rapid detection of wheat blast and other important plant diseases in the field.

Nascent Polypeptide-Associated Complex Involved in the Development and Pathogenesis of Fusarium graminearum on Wheat

Reliable knowledge on pathogenic agents contributes to effective plant protection.For most plant pathogens,maintaining protein homeostasis(proteostasis)is essential for unfolding the cellular functions to survive and thrive.However,the fungal proteins involved in proteostasis remain poorly characterized in the process of pathogenesis.In this study,we characterized the function of the nascent polypeptideassociated complex(NAC)in Fusarium graminearum(F.graminearum)(FgNAC),one of the top 10 fungal pathogens with predominant scientific/economic importance.We found that FgNACa,a subunit of FgNAC,manifests high structural and functional similarity to its homologous counterparts in yeast and other species.The mutants of F.graminearum lacking NACa are viable but suffer significant defects in vegetative growth,conidial production,and pathogenesis.In addition,we show here that FgNACa can interact with another subunit of NAC(FgNACb)in a yeast-two-hybrid assay.The subcellular localization results show that FgNACa and FgNACb are predominantly localized in the cytoplasm.Future studies should focus on deciphering the mechanism by which NAC orchestrates protein biogenesis and consequentially modulates development and pathogenesis.

Anti-tumor Immunity of Gene Vaccine with Nucleofection Technology

OBJECTIVE To observe enhancement of anti-tumor immunity by gene vaccine using nucleofection technology METHODS The technique of nucleofection was used to transfer effectively plasmid DNA into immature dendritic cells （iDCs）; we studied immune responses regulated by DNA vaccine using real-time quantitative polymerase chain reaction （PCR） and western-blotting to optimize the follow-up lymphocyte activation. The anti-tumor capacity of lymphocytes primed by DCs was analyzed using lactate dehydrogenase with a non-radioactive cytotoxicity assay.

The ANIP1-OsWRKY62 module regulates both basal defense and Pi9-mediated immunity against Magnaporthe oryzae in rice

During effector-triggered immunity(ETI)against the devastating rice blast pathogen Magnaporthe oryzae,Pi9 functions as an intracellular resistance protein sensing the pathogen-secreted effector AvrPi9 in rice.Importantly,the underlying recognition mechanism(s)between Pi9 and AvrPi9 remains elusive.In this study,We identified a rice ubiquitin-like domain-containing protein(UDP),AVRPI9-INTERACTING PROTEIN 1(ANP1),which is directly targeted by AvrPi9 and also binds to Pi9 in plants.Phenotypic analysis of anip1 mu-tants and plants overexpressing ANIP1 revealed that ANIP1 negatively modulates rice basal defense against M.oryzae.ANiP1 undergoes 26S proteasome-mediated degradation,which can be blocked by both AvrPi9 and Pi9.Moreover,ANIP1 physically associates with the rice WRKY transcription factor OsWRKY62,which also interacts with AvrPi9 and Pi9 in plants.In the absence of Pi9,ANIP1 negatively regulates OsWRKY62 abundance,which can be promoted by AvrPi9.Accordingly,knocking out of OsWRKY62 in a non-Pi9 back-ground decreased immunity against M.oryzae.However,we also observed that OsWRKY62 plays negative roles in defense against a compatible M.oryzae strain in Pi9-harboring rice.Pi9 binds to ANiP1 and OsWRKY62 to form a complex,which may help to keep Pi9 in an inactive state and weaken rice immunity.Furthermore,using competitive binding assays,we showed that AvrPi9 promotes Pi9 dissociation from ANiP1,which could be an important step toward ETI activation.Taken together,our results reveal an immune strategy whereby a UDP-WRKY module,targeted by a fungal effector,modulates rice immunity in distinct ways in the presence or absence of the corresponding resistance protein.

Harnessing nanobodies to expand the recognition spectrumof plant NLRs for diverse pathogens

The strategy to expand the recognition spectrum of plant nucleotide-binding domain leucine-richrepeat (NLR) proteins by modifying their recognition sequences is generally limited and oftenunsuccessful. Kourelis et al. introduced a groundbreaking approach for generating a customizedimmune receptor, called Pikobody. This method involves integrating a nanobody domain of a fluorescent protein (FP) into a plant NLR. Their research demonstrates that the resulting Pikobody successfully initiates an immune response against diverse pathogens when exposed to the corresponding FP.

Recent Progress in Understanding PAMP- and Effector-Triggered Immunity against the Rice Blast Fungus Magnaporthe oryzae

Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most destructive diseases of rice worldwide. The rice-M, oryzae pathosystem has become a model in the study of plant-fungal interactions because of its scientific advancement and economic importance. Recent studies have identified a number of new pathogen- associated molecular patterns （PAMPs） and effectors from the blast fungus that trigger rice immune responses upon perception. Interaction analyses between avirulence effectors and their cognate resistance proteins have provided new insights into the molecular basis of plant-fungal interactions. In this review, we summarize the recent research on the characterization of those genes in both M. oryzae and rice that are important for the PAMP- and effector-triggered immunity recognition and signaling processes. We also discuss future directions for research that will further our understanding of this pathosystem.

Two VOZ transcription factors link an E3 ligase and an NLR immune receptor to modulate immunity in rice

Nucleotide-binding leucine-rich repeat(NLR)proteins play critical roles in plant immunity.However,how NLRs are regulated and activate defense signaling is not fully understood.The rice(Oryza sativa)NLR receptor Piz-t confers broad-spectrum resistance to the fungal pathogen Magnaporthe oryzae and the RING-type E3 ligase AVRPIZ-T INTERACTING PROTEIN 10(APIP10)negatively regulates Piz-t accumulation.In this study,we found that APIP10 interacts with two rice transcription factors,VASCULAR PLANT ONEZINC FINGER 1(OsVOZ1)and OsVOZ2,and promotes their degradation through the 26S proteasome pathway.OsVOZ1 displays transcriptional repression activity while OsVOZ2 confers transcriptional activation activity in planta.The osvoz1 and osvoz2 single mutants display modest but opposite M.oryzae resistance in the non-Piz-t background.However,the osvoz1 osvoz2 double mutant exhibits strong dwarfism and cell death,and silencing of both genes via RNA interference also leads to dwarfism,mild cell death,and enhanced resistance to M.oryzae in the non-Piz-t background.Both OsVOZ1 and OsVOZ2 interact with Piz-t.Double silencing of OsVOZ1 and OsVOZ2 in the Piz-t background decreases Piz-t protein accumulation and transcription,reactive oxygen species-dependent cell death,and resistance to M.oryzae containing AvrPiz-t.Taken together,these results indicate that OsVOZ1 and OsVOZ2 negatively regulate basal defense but contribute positively to Piz-t-mediated immunity.

Molecular Basis of Disease Resistance and Perspectives on Breeding Strategies for Resistance Improvement in Crops

Crop diseases are major factors responsible for substantial yield losses worldwide,which affects global food security.The use of resistance(R)genes is an effective and sustainable approach to controlling crop diseases.Here,we review recent advances on R gene studies in the major crops and related wild species.Current understanding of the molecular mechanisms underlying R gene activation and signaling,and susceptibility(S)gene-mediated resistance in crops are summarized and discussed.Furthermore,we propose some new strategies for R gene discovery,how to balance resistance and yield,and how to generate crops with broad-spectrum disease resistance.With the rapid development of new genome-editing technologies and the availability of increasing crop genome sequences,the goal of breeding next-generation crops with durable resistance to pathogens is achievable,and will be a key step toward increasing crop production in a sustainable way.

Recent Advances in Cloning and Characterization of Disease Resistance Genes in Rice

Rice diseases caused by fungi, bacteria and viruses are one of the major constraints for sustainable rice （Oryza sativa L.） production worldwide. The use of resistant cultivars is considered the most economical and effective method to control rice diseases. In the last decade, a dozen resistance genes against the fungal pathogen Magnaporthe grisea and the bacterial pathogen Xanthomonas oryzae pv. oryzae have been cloned. Approximately half of them encode nuclear binding site （NBS） and leucine rich repeat （LRR）-containing proteins, the most common type of cloned plant resistance genes. Interestingly, four of them encode novel proteins which have not been identified in other plant species, suggesting that unique mechanisms might be involved in rice defense responses. This review summarizes the recent advances in cloning and characterization of disease resistance genes in rice and presents future perspectives for in-depth molecular analysis of the function and evolution of rice resistance genes and their interaction with avirulence genes in pathogens.

Surgical complexity and prognostic outcome of small volume renal cell carcinoma with high-level venous tumor thrombus and large volume renal cell carcinoma with low-level thrombus

Background:Radical nephrectomy with thrombectomy is one of the most difficult and complicated urological operations.But the roles of renal tumor volume and thrombus level in surgical complexity and prognostic outcome are not clear.This study aimed to evaluate the surgical complexity and prognostic outcome between the volume of renal cell carcinoma (RCC) and the level of venous tumor thrombus.Methods:The clinical data of 67 RCC cases with renal vein or inferior vena cava (IVC) tumor thrombus from January 2015 to May 2018 were retrospectively analyzed.Among these 67 cases,21 (31.3%) were small tumors with high-level thrombus (tumor ≤7 cm in diameter and thrombus Neves Level Ⅱ-Ⅳ),while 46 (68.7%) were large tumors with low-level thrombus group (tumor >7 cm in diameter and thrombus Level 0-Ⅰ).Clinical features,operation details,and pathology data were collected.Univariable and multivariable logistic regression analyses were applied to evaluate the risk factors for small tumor with high-level thrombus.Results:Patients with small tumors and high-level thrombus were more likely to have longer operative time (421.9 ± 135.1 min vs.282.2 ± 101.9 min,t=4.685,P < 0.001),more surgical bleeding volume (1200 [325,2900] mL vs.500 [180,1000] mL,U =270.000,P =0.004),more surgical blood transfusion volume (800 [0,1400] mL vs.0 [0,800] mL,U =287.500,P =0.004),more plasma transfusion volume (0 [0,800] mL vs.0 [0,0] mL,U =319.000,P =0.004),higher percentage of open operative approach (76.2% vs.32.6%,x2 =11.015,P =0.001),higher percentage of IVC resection (33.3% vs.0%,x2 =17.122,P < 0.001),and higher percentage of post-operative complications (52.4% vs.19.6%,x2 =7.415,P =0.010) than patients with large tumors and low-level thrombus.In multivariate analysis,decreased hemoglobin (Hb)(odds ratio [OR]:0.956,95 % confidence interval [CI]:0.926-0.986,P =0.005) and non-sarcomatoid differentiation (OR:0.050,95% CI:0.004-0.664,P =0.023) were more likely to form small tumors with high-level tumor thrombus rather than large tumor with small tumor thrombus.The estimated mean cancerspecific survival times of small tumor with high-level thrombus and large tumor with low-level thrombus were 31.6 ± 3.8 months and 32.5 ± 2.9 months,without statistical significance (P =0.955).After univariate and multivariate Cox proportional hazard survival regression analyses,only distant metastasis (hazard ratio [HR]:3.839,P =0.002),sarcomatoid differentiation (HR:7.923,P < 0.001),alkaline phosphatase (HR:2.661,P =0.025),and severe post-operative complications (HR:10.326,P =0.001) were independent predictors of prognosis.Conclusions:The level of the tumor thrombus was more important than the diameter of the primary kidney tumor in affecting the complexity of surgery.In the same T3 stage,neither the renal tumor diameter nor the tumor thrombus level was an independent risk factor for prognosis.

An Oryza-specific hydroxycinnamoyl tyramine gene cluster contributes to enhanced disease resistance

Genomic clustering of non-homologous genes for the biosynthesis of plant defensive compounds is an emerging theme, but insights into their formation and physiological function remain limited. Here we report the identification of a newly discovered hydroxycinnamoyl tyramine(HT) gene cluster in rice.This cluster contains a pyridoxamine 50-phosphate oxidase(Os PDX3) producing the cofactor pyridoxal50-phosphate(PLP), a PLP-dependent tyrosine decarboxylase(Os Ty DC1), and two duplicated hydroxycinnamoyl transferases(Os THT1 and Os THT2). These members were combined to represent an enzymological innovation gene cluster. Natural variation analysis showed that the abundance of the toxic tyramine intermediate of the gene cluster among different rice accessions is mainly determined by the coordinated transcription of Os Ty DC1 and Os THT1. Further pathogen incubation assays demonstrated that the end products of the HT gene cluster displayed enhanced resistance to the bacterial pathogen Xanthomonas oryzae pv. Oryzae(Xoo) and fungal pathogen Magnaporthe oryzae(M. oryzae), and the enhanced resistance is associated with the boost of phytoalexins and the activation of defense response. The unique presence of the HT gene cluster in Oryza AA genome, together with the enrichment of transposon elements within this gene cluster region, provides an evolutionary background to accelerate cluster member combinations. Our study not only discovered a gene cluster involved in the phenylpropanoid metabolism but also addressed the key aspects of gene cluster formation. In addition, our results provide a new metabolic pool for plant defense against pathogens.

PAPP2C Interacts with the Atypical Disease Resistance Protein RPW8.2 and Negatively Regulates Salicylic Acid-Dependent Defense Responses in Arabidopsis

Many fungal and oomycete pathogens differentiate a feeding structure named the haustorium to extract nutrition from the plant epidermal cell. The atypical resistance （R） protein RPW8.2 activates salicylic acid （SA）-dependent, haustorium-targeted defenses against Golovinomyces spp., the causal agents of powdery mildew diseases on multiple plant species. How RPW8.2 activates defense remains uncharacterized. Here, we report that RPWS.2 interacts with the phytochrome-associated protein phosphatase type 2C （PAPP2C） in yeast and in planta as evidenced by co- immunoprecipitation and bimolecular fluorescence complementation assays. Down-regulation of PAPP2C by RNA interfer- ence （RNAi） in Col-0 plants lacking RPWS.2 leads to leaf spontaneous cell death and enhanced disease resistance to powdery mildew via the SA-dependent signaling pathway. Moreover, down-regulation of PAPP2C by RNAi in the RPW8.2 background results in strong HR-like cell death, which correlates with elevated RPWS.2 expression. We further demonstrate that hemagglutinin （HA）-tagged PAPP2C prepared from tobacco leaf cells transiently transformed with HA-PAPP2C possesses phosphatase activity. In addition, silencing a rice gene （Os04g0452000） homologous to PAPP2C also results in spontaneous cell death in rice. Combined, our results suggest that RPW8.2 is functionally connected with PAPP2C and that PAPP2C negatively regulates SA-dependent basal defense against powdery mildew in Arabidopsis.

Phenylalanine ammonia lyases mediate broad-spectrum resistance to pathogens and insect pests in plants

Phenylalanine ammonia lyases(PALs)are pivotal enzymes for the biosynthesis of lignin,salicylic acid(SA),and other phenylalanine-derived metabolites.Although the functions of PAL genes in plant defense have been studied for over two decades[1],how these genes regulate plant immunity remains obscure.Rice blast(caused by the fungal pathogen Magnaporthe oryzae),bacterial blight(caused by the bacterial pathogen Xanthomonas oryzae pv oryzae or Xoo),and the insect pest brown planthopper(BPH)(Nilaparvata lugens Stål,Hemiptera,Delphacidae)are the most serious threats to global rice production and food security[2,3].

A monocot-specific hydroxycinnamoylputrescine gene cluster contributes to immunity and cell death in rice

Phenolamides(PAs), a diverse group of specialized metabolites, including hydroxycinnamoylputrescine(HP), hydroxycinnamoylagmatine, and hydroxycinnamoyltryptamine, are important in plant resistance to biotic stress. However, the genes involved in the biosynthesis and modulation of PAs have not been fully elucidated. This study identified an HP biosynthetic gene cluster in rice(Oryza sativa) comprising one gene(Os ODC) encoding a decarboxylase and two tandem-duplicated genes(Os PHT3 and Os PHT4)encoding putrescine hydroxycinnamoyl acyltransferases coexpressed in different tissues. Os ODC catalyzes the conversion of ornithine to putrescine, which is used in HP biosynthesis involving Os PHT3 and Os PHT4. Os PHT3 or Os PHT4 overexpression causes HP accumulation and cell death and putrescine hydroxycinnamoyl acyltransferases(PHT) activity-dependent resistance against the fungal pathogen Magnaporthe oryzae. Os ODC overexpression plants also confer enhanced resistance to M. oryzae.Notably, the basic leucine zipper transcription factor APIP5, a negative regulator of cell death, directly binds to the Os PHT4 promoter, repressing its transcription. Moreover, APIP5 suppression induces Os PHT4 expression and HP accumulation. Comparative genomic analysis revealed that the HP biosynthetic gene cluster is conserved in monocots. These results characterized a previously unidentified monocot-specific gene cluster that is involved in HP biosynthesis and contributes to defense and cell death in rice.

The COI1 and DFR Genes are Essential for Regulation of Jasmonate-lnduced Anthocyanin Accumulation in Arabidopsis

Jasmonates （JAs） are a class of plant hormones that play important roles in the regulation of plant development and plant defense. It has been shown that Arabidopsis plants produce much higher levels of anthocyanins when treated exogenously with methyl jasmonate （MeJA）. However, a molecular link between the JA response and anthocyanin production has not been determined. The CORONATINE INSENTITIVE1 （COI1） gene is a key player in the regulation of many JA-related responses. In the present study, we demonstrate that the COI1 gene is also required for the JA-induced accumulation of anthocyanins in Arabidopsis. Furthermore, the MeJA-inducible expression of DIHYDROFLAVONOL REDUCTASE （DFR）, an essential component in the anthocyanin biosynthesis pathway, was completely eliminated in the coil mutant. Jasmonateinduced anthocyanin accumulation was found to be independent of auxin signaling. The present results indicate that the expression of both COI1 and DFR genes is required for the regulation of JA-induced anthocyanin accumulation and that DFR may be a key downstream regulator for this process.

Engineering broad-spectrum disease-resistant rice by editing multiple susceptibility genes

Rice blast and bacterial blight are important diseases of rice(Oryza sativa)caused by the fungus Magnaporthe oryzae and the bacterium Xanthomonas oryzae pv.oryzae(Xoo),respectively.Breeding rice varieties for broadspectrum resistance is considered the most effective and sustainable approach to controlling both diseases.Although dominant resistance genes have been extensively used in rice breeding and production,generating diseaseresistant varieties by altering susceptibility(S)genes that facilitate pathogen compatibility remains unexplored.Here,using CRISPR/Cas9 technology,we generated loss-of-function mutants of the S genes Pi21 and Bsr-d1 and showed that they had increased resistance to M.oryzae.We also generated a knockout mutant of the S gene Xa5 that showed increased resistance to Xoo.Remarkably,a triple mutant of all three S genes had significantly enhanced resistance to both M.oryzae and Xoo.Moreover,the triple mutant was comparable to the wild type in regard to key agronomic traits,including plant height,effective panicle number per plant,grain number per panicle,seed setting rate,and thousand-grain weight.These results demonstrate that the simultaneous editing of multiple S genes is a powerful strategy for generating new rice varieties with broadspectrum resistance.

SINA E3 Ubiquitin Ligases:Versatile Moderators of Plant Growth and Stress Response

Protein degradation mediated by the ubiquitin-proteasome system(UPS)is involved in many cellular processes in animals and plants.In the UPS,E3 ligases(E3s)are essential for recognizing target proteins and promoting substrate degradation.One E3 ligase,SINA(seven in absentia),which was first identified in Drosophila,is involved in a variety of signaling transduction networks in both animals and plants.Here we discuss recent advances in understanding SINA?mediated regulation of plant growth and responses to abiotic and biotic stresses.