Background:Alterations in splicing factors contribute to aberrant alternative splicing(AS),which subsequently promotes tumor progression.The splicing factor polypyrimidine tract binding protein 1(PTBP1)has been shown ...Background:Alterations in splicing factors contribute to aberrant alternative splicing(AS),which subsequently promotes tumor progression.The splicing factor polypyrimidine tract binding protein 1(PTBP1)has been shown to facilitate cancer progression by modulating oncogenic variants.However,its specific role and underlying mechanisms in hepatocellular carcinoma(HCC)remain to be elucidated.Methods:PTBP1 expression was evaluated in HCC tissues and cell lines.Subsequently,cells were transfected with vectors designed for PTBP1 overexpression or downregulation.The biological function of PTBP1 was assessed in vitro and in vivo using MTS assays,colony formation assays,transwell assays,xenograft formation,tail vein injection,and orthotopic models.Transcriptome analysis was conducted to elucidate the underlying molecular mechanisms.Results:Our findings demonstrated that PTBP1 exhibited elevated expression in HCC cell lines and tissues.Furthermore,its expression positively correlated with overall and disease-free survival rates,as well as tumor grade and stage.PTBP1 knockdown reduced HCC cell proliferation,migration,and invasion in vitro and suppressed hepatocarcinoma xenograft growth and infiltration in vivo.RNA sequencing(RNA-Seq)analysis identified the AS events associated with PTBP1.PTBP1 functionally enhanced cell proliferation,invasion,and migration by modulating the AS of the microtubule-associated protein tau(MAPT)gene and promoting oncogene expression.Notably,the dysregulation of MAPT splicing coincided with increased PTBP1 expression in HCC.Conclusions:PTBP1-guided AS of the MAPT gene enhances tumorigenicity in HCC through activation of the MAPK/ERK pathways.展开更多
Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intro...Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intron splicing and its role in maize kernel development.PPR21 is a typical P-type PPR protein targeted to mitochondria.The ppr21 mutants are arrested in embryogenesis and endosperm development,leading to embryo lethality.Null mutations of PPR21 reduce the splicing efficiency of nad2 intron 1,2,and 4 and impair the assembly and activity of mitochondrial complex I.Previous studies show that the P-type PPR protein EMP12 is required for the splicing of identical introns.However,our protein interaction analyses reveal that PPR21 does not interact with EMP12.Instead,both PPR21 and EMP12 interact with the small MutS-related(SMR)domain-containing PPR protein 1(PPR-SMR1)and the short P-type PPR protein 2(SPR2).PPR-SMR1 interacts with SPR2,and both proteins are required for the splicing of many introns in mitochondria,including nad2 intron 1,2,and 4.These results suggest that a PPR21-(PPR-SMR1/SPR2)-EMP12 complex is involved in the splicing of nad2 introns in maize mitochondria.展开更多
In this study,we examine the problem of sliced inverse regression(SIR),a widely used method for sufficient dimension reduction(SDR).It was designed to find reduced-dimensional versions of multivariate predictors by re...In this study,we examine the problem of sliced inverse regression(SIR),a widely used method for sufficient dimension reduction(SDR).It was designed to find reduced-dimensional versions of multivariate predictors by replacing them with a minimally adequate collection of their linear combinations without loss of information.Recently,regularization methods have been proposed in SIR to incorporate a sparse structure of predictors for better interpretability.However,existing methods consider convex relaxation to bypass the sparsity constraint,which may not lead to the best subset,and particularly tends to include irrelevant variables when predictors are correlated.In this study,we approach sparse SIR as a nonconvex optimization problem and directly tackle the sparsity constraint by establishing the optimal conditions and iteratively solving them by means of the splicing technique.Without employing convex relaxation on the sparsity constraint and the orthogonal constraint,our algorithm exhibits superior empirical merits,as evidenced by extensive numerical studies.Computationally,our algorithm is much faster than the relaxed approach for the natural sparse SIR estimator.Statistically,our algorithm surpasses existing methods in terms of accuracy for central subspace estimation and best subset selection and sustains high performance even with correlated predictors.展开更多
目的探讨虚拟仿真结合改良自我导向、问题导向、终身学习、综合临床案例练习(selfdirected,problem-oriented,lifelong learning,integrated clinical case exercise,SPLICE)教学法对临床医学专硕生批判性思维能力的影响。方法选取2024...目的探讨虚拟仿真结合改良自我导向、问题导向、终身学习、综合临床案例练习(selfdirected,problem-oriented,lifelong learning,integrated clinical case exercise,SPLICE)教学法对临床医学专硕生批判性思维能力的影响。方法选取2024年1—6月在锦州医科大学附属第一医院皮肤科进行住院医师规范化培训(简称“住培”)的64名2023级临床医学专硕生为研究对象。采用随机分组法将其分为试验组(n=32)和对照组(n=32)。试验组采用虚拟仿真结合改良SPLICE教学,对照组采用传统教学方式。比较两组学生批判性思维能力、学业自我效能感、理论考核和临床操作技能考核成绩。结果试验组医学专硕生的批判性思维能力、学业自我效能感、理论考核和临床操作技能考核成绩均高于对照组,差异具有统计学意义(均P<0.001)。结论虚拟仿真结合改良SPLICE教学法有助于提升医学专硕生的批判性思维能力与学业自我效能感,有利于其更好地掌握专业理论和临床操作技能,值得在临床教学中进一步推广应用。展开更多
ObjectivesThe PTPRQ gene is essential for preserving the structure and function of stereocilia in inner ear.However,research on splicing mutations within this gene is limited.This study aims to investigate novel splic...ObjectivesThe PTPRQ gene is essential for preserving the structure and function of stereocilia in inner ear.However,research on splicing mutations within this gene is limited.This study aims to investigate novel splicing mutations in PTPRQ,clarify their molecular mechanisms,and provide new insights into the genetic factors associated with hearing loss,ultimately enhancing diagnostic accuracy.MethodClinical data and peripheral blood samples were obtained from members of a family with congenital hearing loss.Variants were identified through high-throughput sequencing and confirmed by Sanger sequencing to ensure genealogical co-segregation.The splicing effects of PTPRQ variants were evaluated using bioinformatics tools and minigene assays.ResultsWe used whole exome sequencing to identify novel double compound heterozygous splice-altering variants(c.5426+1 G>A and c.6603-3 T>G)in the PTPRQ gene with DFNB84A.We molecularly characterized these variants,and they were found to co-segregate with the disease within the family.Minigene assays and Sanger sequencing confirmed that the c.6603-3 T>G variant caused exon 43 skipping,resulting in a frameshift mutation(p.Ser2201ArgfsTer112).Further bioinformatic analysis supported these findings.ConclusionsThis study identifies a novel compound heterozygous splicing variant in the PTPRQ gene in a Chinese family with DFNB84A,expanding the known spectrum of PTPRQ mutations.These findings enhance the understanding of PTPRQ-related hearing loss and may aid in early diagnosis,prevention,and therapeutic strategies.展开更多
Caspases,which play key roles in cell apoptosis,undergo alternative splicing to form different splicing variants that can regulate the apoptotic process.Lepidopteran insect caspases undergo alternative splicing,althou...Caspases,which play key roles in cell apoptosis,undergo alternative splicing to form different splicing variants that can regulate the apoptotic process.Lepidopteran insect caspases undergo alternative splicing,although the functions of their splicing variants are still unclear.The Spodoptera exigua caspase-5(SeCaspase-5)gene was cloned and found to produce four different splicing variants with different gene sequences and protein functional domains,which were named SeCaspase-5a,SeCaspase-5b,SeCaspase-5c and SeCaspase-5d.Overexpression of these variants in S.exigua cells(Se-3)showed that SeCaspase-5a had a proapoptotic function,whereas SeCaspase-5b,SeCaspase-5c and SeCaspase-5d did not.Semi-qPCR analysis revealed that the expression of the SeCaspase-5 variants significantly differed during Autographa californica multiple nucleopolyhedrovirus(AcMNPV)infection.Furthermore,the SeCaspase-5 variants were constructed into the AcMNPV bacmid and transfected into Se-3 cells,which revealed that SeCaspase-5a promoted cell apoptosis and reduced virus production,whereas SeCaspase-5b,SeCaspase-5c and SeCaspase-5d did not promote cell apoptosis but instead increased virus production.Moreover,an analysis of the interactions between the SeCaspase-5 variants revealed that SeCaspase-5a directly interacted with SeCaspase-5b,SeCaspase-5c and SeCaspase-5d.Coexpression of these variants in Se-3 cells also revealed that SeCaspase-5b,SeCaspase-5c and SeCaspase-5d inhibited the proapoptotic function of SeCaspase-5a,resulting in a reduction in the percentage of apoptotic cells by about 20%.These results indicate that SeCaspase-5 undergoes alternative splicing and is involved in regulating the apoptosis induced by baculovirus infection.These findings increase our understanding of the functions of lepidopteran insect caspases and provide new insights into the mechanism of host-cell apoptosis induced by baculoviruses.展开更多
The formation of root system architecture(RSA)plays a crucial role in plant growth.OsDRO1 is known to have a function in controlling RSA in rice,however,the role of potato StDRO2,a homolog of rice OsDRO1,in root growt...The formation of root system architecture(RSA)plays a crucial role in plant growth.OsDRO1 is known to have a function in controlling RSA in rice,however,the role of potato StDRO2,a homolog of rice OsDRO1,in root growth remains unclear.In this study,we obtained potato dro2 mutant lines by Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated 9(CRISPR/Cas9)-mediated genome editing system.The mutant lines were generated from a splicing defect of the StDRO2 intron 1,which causes a nonsense mutation in StDRO2.Furthermore,the secondary structure of StDRO2 mRNA analyzed with RNAfold Web Server was altered in the dro2 mutant.Mutation of StDRO2 conveys potato adaptation through changing the RSA via alteration of auxin transport under drought stress.The potato dro2 lines showed higher plant height,longer root length,smaller root growth angle and increased tuber weight than the wild-type.The alteration of RSA was associated with a disturbance of IAA distribution in the dro2 mutant,and the levels of StPIN7 and StPIN10 detected by using real-time PCR were up-regulated in the roots of potato dro2 lines grown under drought stress.Moreover,the microRNAs(miRNAs)PmiREN024536 and PmiREN024486 targeted the StDRO2 gene,and auxin positively and negatively regulated the expression of StDRO2 and the miRNAs PmiREN024536 and PmiREN024486,respectively,in the potato roots.Our data shows that a regulatory network involving auxin,StDRO2,PmiREN024536 and PmiREN024486 can control RSA to convey potato fitness under drought stress.展开更多
Heat stress is a major threat to maize(Zea mays L.)production worldwide.Heat shock transcription factors(HSFs)play vital roles in plant responses to heat stress.However,the molecular and genetic mechanisms underlying ...Heat stress is a major threat to maize(Zea mays L.)production worldwide.Heat shock transcription factors(HSFs)play vital roles in plant responses to heat stress.However,the molecular and genetic mechanisms underlying HSF-meditated thermotolerance in maize remain largely unexplored.In this study,we demonstrate that the alternative splicing of ZmHsf23 modulates heat stress tolerance in maize.Hsf23 produced two functional transcripts,Hsf23L and Hsf23S,which differ by the presence of a cryptic mini-exon in Hsf23L that is spliced out in Hsf23S.Both transcripts were strongly induced by heat stress.Mutants lacking Hsf23L alone(hsf23l)or both Hsf23L and Hsf23S(hsf23l23s)exhibited increased susceptibility to heat stress,whereas overexpression of Hsf23S enhanced heat stress tolerance in maize.Subsequently,we found that Hsf23S positively regulates heat stress tolerance by directly activating the transcription of three sHSP genes(Hsp16.9,Hsp17.2,and Hsp18a)and TIL1 gene.In addition,Hsf23L physically interacted with Hsf23S and enhanced the transcriptional activation of Hsf23S on the sHSPs and TIL1 promoters.Notably,genetic analysis suggested that co-overexpression of Hsf23L and Hsf23S further improves heat tolerance of the transgenic plants.Taken together,these results reveal two splicing variants of ZmHsf23 cooperatively regulate maize heat tolerance,thus highlighting potential value of ZmHsf23 in breeding heat-tolerant maize varieties.展开更多
Background:Glioblastoma(GBM)is one of the most malignant types of central nervous system tumors.Oxygen deprivation in the tumor microenvironment is thought to be an important factor in promoting GBM progression.Howeve...Background:Glioblastoma(GBM)is one of the most malignant types of central nervous system tumors.Oxygen deprivation in the tumor microenvironment is thought to be an important factor in promoting GBM progression.However,the mechanisms of hypoxia-promoted tumor progression remain elusive.Methods:Alternative splicing of diacylglycerol kinase gamma(DGKG)-Δexon13 was amplified and verified by PCR-Sanger sequencing.The functions of DGKG and DGKG-Δexon13 were analyzed by Cell counting kit-8(CCK-8),Transwell,Matrigeltranswell experiments,and in vivo orthotropic GBM animal models.Transcriptome analyses were done to find out the regulated genes.Results:In this study,we found that a new transcript DGKG-Δexon13 was generated in GBM under hypoxia via alternative splicing.Moreover,the results of CCK-8,Transwell,and Matrigel-transwell experiments showed that the proliferation,migration,and invasion abilities of U87-MG and T98G were decreased after DGKG knockdown.Compared to wild-type DGKG,DGKG-Δexon13 overexpression significantly promoted cellular proliferation,migration,and invasion abilities in GBM.Furthermore,in vivo,orthotropic GBM animal models analysis showed that the tumor volumes were much smaller in the DGKG knockdown group.However,the tumor sizes in the DGKG and DGKG-Δexon13 rescue groups were restored,especially in the DGKG-Δexon13 group.Transcriptome analysis revealed that MORC1,KLHDC7B,ATP1A2,INHBE,TMEM119,and FGD3 were altered significantly when DGKG was knocked down.IL-16,CCN2,and EFNB3 were specifically regulated by DGKG-Δexon13.Conclusions:Our study found that hypoxia-induced alternative splicing transcript DGKG-Δexon13 promotes GBM proliferation and infiltration,which might provide a new potential target for the clinical treatment and diagnosis of GBM.展开更多
Starch biosynthesis is a complex process that relies on the coordinated action of multiple enzymes.Resistant starch is not digested in the small intestine,thus preventing a rapid rise in the glycemic index.Starch synt...Starch biosynthesis is a complex process that relies on the coordinated action of multiple enzymes.Resistant starch is not digested in the small intestine,thus preventing a rapid rise in the glycemic index.Starch synthase 2a(SS2a)is a key enzyme in amylopectin biosynthesis that has significant effects on starch structure and properties.In this study,we identified an ss2a null mutant(M3-1413)with a single base mutation from an ethyl methane sulfonate(EMS)-mutagenized population of barley.The mutation was located at the 3'end of the first intron of the RNA splicing receptor(AG)site,and resulted in abnormal RNA splicing and two abnormal transcripts of ss2a,which caused the inactivation of the SS2a gene.The starch structure and properties were significantly altered in the mutant,with M3-1413 containing lower total starch and higher amylose and resistant starch levels.This study sheds light on the effect of barley ss2a null mutations on starch properties and will help to guide new applications of barley starch in the development of nutritious food products.展开更多
Myocardial infarction(MI)is characterized by focal necrosis resulting from prolonged myocardial ischemia due to coronary artery obstruction.Vascular reconstruction following MI is crucial for improving cardiac functio...Myocardial infarction(MI)is characterized by focal necrosis resulting from prolonged myocardial ischemia due to coronary artery obstruction.Vascular reconstruction following MI is crucial for improving cardiac function and preventing recurrent infarction.This study investigates the interaction between macrophages and endothelial cells in angiogenesis mediated by nicotinamide mononucleotide(NMN)-induced secretion of macrophage-derived exosomes.We focus on the role of U2 small nuclear RNA auxiliary factor 1(U2af1)gene,a member of the splicing factor serine and arginine(SR)gene family,in the regulation of angiogenesis.Through cardiac ultrasound,Masson staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,Microfil vascular perfusion,and platelet and endothelial cell adhesion molecule 1(CD31)immunofluorescence staining,extracellular vesicles from NMN-stimulated macrophages were shown to exert a protective effect in MI,with proteomic analysis identifying U2AF1 as a candidate protein involved in MI protection.Plasma U2AF1 levels were measured in 70 MI patients,revealing significantly lower levels in individuals with poor coronary collateral vessel(CCV;Rentrop scores 0–1)than in those with good CCV(Rentrop scores 2–3).In both myocardial and hindlimb ischemia mouse models,overexpression of endothelial cell-specific adenoviral overexpression U2AF1 promoted angiogenesis in the heart and hindlimbs and improved cardiac function after MI.Mechanistic studies demonstrated that U2AF1 regulates the alternative splicing(AS)of Yes1-associated transcriptional regulator(Yap1)gene,influencing post-MI angiogenesis and cardiac function recovery.Collectively,our clinical findings suggest that U2AF1 may serve as a therapeutic target for coronary collateral angiogenesis following MI.Given the low immunogenicity and high biosafety of exosomes,this study provides a foundational basis and translational potential for exosome-based therapies in MI treatment.展开更多
OCT4 is one of the key transcription factors in maintaining the pluripotency and self-renewal of embryonic stem （ES） cells.Human OCT4 can generate two isoforms OCT4A and OCT4B by alternative splicing.OCT4B1 is a rec...OCT4 is one of the key transcription factors in maintaining the pluripotency and self-renewal of embryonic stem （ES） cells.Human OCT4 can generate two isoforms OCT4A and OCT4B by alternative splicing.OCT4B1 is a recently discovered novel OCT4 spliced variant,which has been considered as a putative marker of stemness.Compared with the OCT4B mRNA,OCT4B1 mRNA is generated by retaining intron 2 as a cryptic exon which contains a TGA stop codon in it.As a result,the protein product of OCT4B1 mRNA could be truncated.Interestingly,we present here that OCT4B1 can indirectly produce the same protein products as OCT4B.We have demonstrated that OCT4B1 mRNA can be spliced into OCT4B mRNA,and encode three protein isoforms.The splicing of OCT4B1 mRNA into OCT4B mRNA can be remarkably inhibited by the mutation of the classical splicing site.Our result suggests that OCT4B mRNA may originate from OCT4B1 mRNA by alternative splicing.展开更多
The shaping form of an untwisted yarn-end for the air splicer is analyzed and then a cosine curve form which will have practically good splicing effect is proposed. The yarn motion in the splicing nozzle by applying h...The shaping form of an untwisted yarn-end for the air splicer is analyzed and then a cosine curve form which will have practically good splicing effect is proposed. The yarn motion in the splicing nozzle by applying hydrodynamics and the splicing principle of the air splicer are also studied.展开更多
The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first comp...The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.展开更多
Amino acids are the primary form of nitrogen utilization in higher plants,mainly transported by amino acid transporters.In this study,we analyzed the natural variation of amino acid transporter-like 4(OsATL4)in rice g...Amino acids are the primary form of nitrogen utilization in higher plants,mainly transported by amino acid transporters.In this study,we analyzed the natural variation of amino acid transporter-like 4(OsATL4)in rice germplasm resources,identified its spatiotemporal expression characteristics,determined its substrate transport,and validated its function using transgenic plants.We found that the promoter sequence of OsATL4 varied across 498 rice varieties.The expression level of OsATL4 was higher in japonica rice,which was negatively correlated with tiller number and grain yield.OsATL4 was highly expressed in the basal part,leaf sheath,stem,and young panicle,with its two splicing variants localized to the cell membrane.OsATL4a(the long splicing variant)had a high affinity for transporting Ser,Leu,Phe,and Thr,while OsATL4b(the short splicing variant)had a high affinity for transporting Ser,Leu,and Phe.Blocking OsATL4 promoted axillary bud outgrowth,rice tillering,and grain yield,whereas overexpression lines exhibited the opposite phenotype.Exogenous application of low concentrations of Ser promoted axillary bud outgrowth in overexpression lines,while high concentrations of Ser inhibited it.Conversely,the mutant lines showed the opposite response.Altered expression of OsATL4 might affect the expression of genes in nitrogen,auxin,and cytokinin pathways.We propose that two splicing variants of OsATL4 negatively regulate rice tillering and yield by mediating the transport of amino acids,making it a significant target for high-yield rice breeding.展开更多
Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,sto...Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.展开更多
RNA splicing normally generates stable splice- junction sequences in viruses that are important in the context of virus mimicry. Potential variability in envelop proteins may occur with point-mutations inducing crypti...RNA splicing normally generates stable splice- junction sequences in viruses that are important in the context of virus mimicry. Potential variability in envelop proteins may occur with point-mutations inducing cryptic splice-junctions, which would remain unrecognized by T-memory cells of higher organisms in vaccine trials. Such aberrant splice- junctions result from evolution-specific non-conser- vation of actual splice-junction sites due to mutations;as such, locations of splice-junctions in a test DNA sequence could only be imprecisely specified. Such impreciseness of splice-junction locations (or cryptic sites) in a sequence is evaluated in this study via “noisy” attributes (with associated stochastics) to the mutated subspace;and, relevant fuzzy considerations are invoked with membership attributes expressed in terms of a spatial signal-to-noise ratio (SSNR). That is, SSNR adopted as a membership function expresses the belongingness of a site-region to exon/intron subspaces. An illustrative example with actual (Dengue 1 viral) DNA data is furnished demonstrating the pursuit developed in predicting aberrant splice-junctions at cryptic sites in the test sequence.展开更多
The growing prevalence of fake images on the Internet and social media makes image integrity verification a crucial research topic.One of the most popular methods for manipulating digital images is image splicing,whic...The growing prevalence of fake images on the Internet and social media makes image integrity verification a crucial research topic.One of the most popular methods for manipulating digital images is image splicing,which involves copying a specific area from one image and pasting it into another.Attempts were made to mitigate the effects of image splicing,which continues to be a significant research challenge.This study proposes a new splicing detectionmodel,combining Sonine functions-derived convex-based features and deep features.Two stages make up the proposed method.The first step entails feature extraction,then classification using the“support vector machine”(SVM)to differentiate authentic and spliced images.The proposed Sonine functions-based feature extraction model reveals the spliced texture details by extracting some clues about the probability of image pixels.The proposed model achieved an accuracy of 98.93% when tested with the CASIA V2.0 dataset“Chinese Academy of Sciences,Institute of Automation”which is a publicly available dataset for forgery classification.The experimental results show that,for image splicing forgery detection,the proposed Sonine functions-derived convex-based features and deep features outperform state-of-the-art techniques in terms of accuracy,precision,and recall.Overall,the obtained detection accuracy attests to the benefit of using the Sonine functions alongside deep feature representations.Finding the regions or locations where image tampering has taken place is limited by the study.Future research will need to look into advanced image analysis techniques that can offer a higher degree of accuracy in identifying and localizing tampering regions.展开更多
Brassica oleracea has been developed into many important crops,including cabbage,kale,cauliflower,broccoli and so on.The genome and gene annotation of cabbage(cultivar JZS),a representative morphotype of B.oleracea,ha...Brassica oleracea has been developed into many important crops,including cabbage,kale,cauliflower,broccoli and so on.The genome and gene annotation of cabbage(cultivar JZS),a representative morphotype of B.oleracea,has been widely used as a common reference in biological research.Although its genome assembly has been updated twice,the current gene annotation still lacks information on untranslated regions(UTRs)and alternative splicing(AS).Here,we constructed a high-quality gene annotation(JZSv3)using a full-length transcriptome acquired by nanopore sequencing,yielding a total of 59452 genes and 75684 transcripts.Additionally,we re-analyzed the previously reported transcriptome data related to the development of different tissues and cold response using JZSv3 as a reference,and found that 3843 out of 11908 differentially expressed genes(DEGs)underwent AS during the development of different tissues and 309 out of 903 cold-related genes underwent AS in response to cold stress.Meanwhile,we also identified many AS genes,including BolLHCB5 and BolHSP70,that displayed distinct expression patterns within variant transcripts of the same gene,highlighting the importance of JZSv3 as a pivotal reference for AS analysis.Overall,JZSv3 provides a valuable resource for exploring gene function,especially for obtaining a deeper understanding of AS regulation mechanisms.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81972771,82173062)the Key Areas Project of Education Department of Guangdong Province(No.2021ZDZX2017)+3 种基金the Tertiary Education Scientific Research Project of Guangzhou Municipal Education Bureau(No.202235387)the Guangzhou Science and Technology Project of Guangzhou Municipal Science and Technology Bureau(No.2023A03J0428)the Natural Science Foundation of Guangdong Province,China(No.2024A1515013082)the Guangdong Basic and Applied Basic Research 21 Foundation(No.2021A1515010403).
文摘Background:Alterations in splicing factors contribute to aberrant alternative splicing(AS),which subsequently promotes tumor progression.The splicing factor polypyrimidine tract binding protein 1(PTBP1)has been shown to facilitate cancer progression by modulating oncogenic variants.However,its specific role and underlying mechanisms in hepatocellular carcinoma(HCC)remain to be elucidated.Methods:PTBP1 expression was evaluated in HCC tissues and cell lines.Subsequently,cells were transfected with vectors designed for PTBP1 overexpression or downregulation.The biological function of PTBP1 was assessed in vitro and in vivo using MTS assays,colony formation assays,transwell assays,xenograft formation,tail vein injection,and orthotopic models.Transcriptome analysis was conducted to elucidate the underlying molecular mechanisms.Results:Our findings demonstrated that PTBP1 exhibited elevated expression in HCC cell lines and tissues.Furthermore,its expression positively correlated with overall and disease-free survival rates,as well as tumor grade and stage.PTBP1 knockdown reduced HCC cell proliferation,migration,and invasion in vitro and suppressed hepatocarcinoma xenograft growth and infiltration in vivo.RNA sequencing(RNA-Seq)analysis identified the AS events associated with PTBP1.PTBP1 functionally enhanced cell proliferation,invasion,and migration by modulating the AS of the microtubule-associated protein tau(MAPT)gene and promoting oncogene expression.Notably,the dysregulation of MAPT splicing coincided with increased PTBP1 expression in HCC.Conclusions:PTBP1-guided AS of the MAPT gene enhances tumorigenicity in HCC through activation of the MAPK/ERK pathways.
基金supported by the National Natural Science Foundation of China(32072126 and 32230075)the Shandong Provincial Natural Science Foundation(ZR2019MC005).
文摘Pentatricopeptide repeat(PPR)proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression.Here,we report the function of PPR21 in mitochondrial intron splicing and its role in maize kernel development.PPR21 is a typical P-type PPR protein targeted to mitochondria.The ppr21 mutants are arrested in embryogenesis and endosperm development,leading to embryo lethality.Null mutations of PPR21 reduce the splicing efficiency of nad2 intron 1,2,and 4 and impair the assembly and activity of mitochondrial complex I.Previous studies show that the P-type PPR protein EMP12 is required for the splicing of identical introns.However,our protein interaction analyses reveal that PPR21 does not interact with EMP12.Instead,both PPR21 and EMP12 interact with the small MutS-related(SMR)domain-containing PPR protein 1(PPR-SMR1)and the short P-type PPR protein 2(SPR2).PPR-SMR1 interacts with SPR2,and both proteins are required for the splicing of many introns in mitochondria,including nad2 intron 1,2,and 4.These results suggest that a PPR21-(PPR-SMR1/SPR2)-EMP12 complex is involved in the splicing of nad2 introns in maize mitochondria.
文摘In this study,we examine the problem of sliced inverse regression(SIR),a widely used method for sufficient dimension reduction(SDR).It was designed to find reduced-dimensional versions of multivariate predictors by replacing them with a minimally adequate collection of their linear combinations without loss of information.Recently,regularization methods have been proposed in SIR to incorporate a sparse structure of predictors for better interpretability.However,existing methods consider convex relaxation to bypass the sparsity constraint,which may not lead to the best subset,and particularly tends to include irrelevant variables when predictors are correlated.In this study,we approach sparse SIR as a nonconvex optimization problem and directly tackle the sparsity constraint by establishing the optimal conditions and iteratively solving them by means of the splicing technique.Without employing convex relaxation on the sparsity constraint and the orthogonal constraint,our algorithm exhibits superior empirical merits,as evidenced by extensive numerical studies.Computationally,our algorithm is much faster than the relaxed approach for the natural sparse SIR estimator.Statistically,our algorithm surpasses existing methods in terms of accuracy for central subspace estimation and best subset selection and sustains high performance even with correlated predictors.
文摘目的探讨虚拟仿真结合改良自我导向、问题导向、终身学习、综合临床案例练习(selfdirected,problem-oriented,lifelong learning,integrated clinical case exercise,SPLICE)教学法对临床医学专硕生批判性思维能力的影响。方法选取2024年1—6月在锦州医科大学附属第一医院皮肤科进行住院医师规范化培训(简称“住培”)的64名2023级临床医学专硕生为研究对象。采用随机分组法将其分为试验组(n=32)和对照组(n=32)。试验组采用虚拟仿真结合改良SPLICE教学,对照组采用传统教学方式。比较两组学生批判性思维能力、学业自我效能感、理论考核和临床操作技能考核成绩。结果试验组医学专硕生的批判性思维能力、学业自我效能感、理论考核和临床操作技能考核成绩均高于对照组,差异具有统计学意义(均P<0.001)。结论虚拟仿真结合改良SPLICE教学法有助于提升医学专硕生的批判性思维能力与学业自我效能感,有利于其更好地掌握专业理论和临床操作技能,值得在临床教学中进一步推广应用。
基金supported in part by the Natural Science Foundation of Shandong Province(no.ZR2022QH373,ZR2022QH292 and ZR2023MH2474).
文摘ObjectivesThe PTPRQ gene is essential for preserving the structure and function of stereocilia in inner ear.However,research on splicing mutations within this gene is limited.This study aims to investigate novel splicing mutations in PTPRQ,clarify their molecular mechanisms,and provide new insights into the genetic factors associated with hearing loss,ultimately enhancing diagnostic accuracy.MethodClinical data and peripheral blood samples were obtained from members of a family with congenital hearing loss.Variants were identified through high-throughput sequencing and confirmed by Sanger sequencing to ensure genealogical co-segregation.The splicing effects of PTPRQ variants were evaluated using bioinformatics tools and minigene assays.ResultsWe used whole exome sequencing to identify novel double compound heterozygous splice-altering variants(c.5426+1 G>A and c.6603-3 T>G)in the PTPRQ gene with DFNB84A.We molecularly characterized these variants,and they were found to co-segregate with the disease within the family.Minigene assays and Sanger sequencing confirmed that the c.6603-3 T>G variant caused exon 43 skipping,resulting in a frameshift mutation(p.Ser2201ArgfsTer112).Further bioinformatic analysis supported these findings.ConclusionsThis study identifies a novel compound heterozygous splicing variant in the PTPRQ gene in a Chinese family with DFNB84A,expanding the known spectrum of PTPRQ mutations.These findings enhance the understanding of PTPRQ-related hearing loss and may aid in early diagnosis,prevention,and therapeutic strategies.
基金funded by the National Natural Science Foundation of China(32202393)the Natural Science Foundation of Shandong Province,China(ZR2021QC190)+1 种基金the Science and Technology Benefiting the People Demonstration Project of Qingdao,China(24-1-8-xdny-10-nsh)the Qingdao Agricultural University High-level Talent Fund,China(663/1120101)。
文摘Caspases,which play key roles in cell apoptosis,undergo alternative splicing to form different splicing variants that can regulate the apoptotic process.Lepidopteran insect caspases undergo alternative splicing,although the functions of their splicing variants are still unclear.The Spodoptera exigua caspase-5(SeCaspase-5)gene was cloned and found to produce four different splicing variants with different gene sequences and protein functional domains,which were named SeCaspase-5a,SeCaspase-5b,SeCaspase-5c and SeCaspase-5d.Overexpression of these variants in S.exigua cells(Se-3)showed that SeCaspase-5a had a proapoptotic function,whereas SeCaspase-5b,SeCaspase-5c and SeCaspase-5d did not.Semi-qPCR analysis revealed that the expression of the SeCaspase-5 variants significantly differed during Autographa californica multiple nucleopolyhedrovirus(AcMNPV)infection.Furthermore,the SeCaspase-5 variants were constructed into the AcMNPV bacmid and transfected into Se-3 cells,which revealed that SeCaspase-5a promoted cell apoptosis and reduced virus production,whereas SeCaspase-5b,SeCaspase-5c and SeCaspase-5d did not promote cell apoptosis but instead increased virus production.Moreover,an analysis of the interactions between the SeCaspase-5 variants revealed that SeCaspase-5a directly interacted with SeCaspase-5b,SeCaspase-5c and SeCaspase-5d.Coexpression of these variants in Se-3 cells also revealed that SeCaspase-5b,SeCaspase-5c and SeCaspase-5d inhibited the proapoptotic function of SeCaspase-5a,resulting in a reduction in the percentage of apoptotic cells by about 20%.These results indicate that SeCaspase-5 undergoes alternative splicing and is involved in regulating the apoptosis induced by baculovirus infection.These findings increase our understanding of the functions of lepidopteran insect caspases and provide new insights into the mechanism of host-cell apoptosis induced by baculoviruses.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.32260085,31860064,31660501,31970609,32260718 and 31901870)the Key Projects of the Applied Basic Research Plan of Yunnan Province(Grant No.202301AS070082)+3 种基金the Start-up fund from Xishuangbanna Tropical Botanical Garden,the‘Top Talents Program in Science and Technology’from Yunnan Province,the Major Science and Technology Project in Yunnan Province(Grant Nos.202102AE090042 and 202202AE090036)the Young and Middle-Aged Academic and Technical Leaders Reserve Talent Program in Yunnan Province(Grant No.202205AC160076)China Postdoctoral Science Foundation(Grant No.2019M653849XB)the High-level Talents Introduction Plan of Yunnan Province-Young Talents Special Project。
文摘The formation of root system architecture(RSA)plays a crucial role in plant growth.OsDRO1 is known to have a function in controlling RSA in rice,however,the role of potato StDRO2,a homolog of rice OsDRO1,in root growth remains unclear.In this study,we obtained potato dro2 mutant lines by Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-Associated 9(CRISPR/Cas9)-mediated genome editing system.The mutant lines were generated from a splicing defect of the StDRO2 intron 1,which causes a nonsense mutation in StDRO2.Furthermore,the secondary structure of StDRO2 mRNA analyzed with RNAfold Web Server was altered in the dro2 mutant.Mutation of StDRO2 conveys potato adaptation through changing the RSA via alteration of auxin transport under drought stress.The potato dro2 lines showed higher plant height,longer root length,smaller root growth angle and increased tuber weight than the wild-type.The alteration of RSA was associated with a disturbance of IAA distribution in the dro2 mutant,and the levels of StPIN7 and StPIN10 detected by using real-time PCR were up-regulated in the roots of potato dro2 lines grown under drought stress.Moreover,the microRNAs(miRNAs)PmiREN024536 and PmiREN024486 targeted the StDRO2 gene,and auxin positively and negatively regulated the expression of StDRO2 and the miRNAs PmiREN024536 and PmiREN024486,respectively,in the potato roots.Our data shows that a regulatory network involving auxin,StDRO2,PmiREN024536 and PmiREN024486 can control RSA to convey potato fitness under drought stress.
基金supported by the National Key Research and Development Program of China(2021YFF1000301)the National Natural Science Foundation of China(31771805)。
文摘Heat stress is a major threat to maize(Zea mays L.)production worldwide.Heat shock transcription factors(HSFs)play vital roles in plant responses to heat stress.However,the molecular and genetic mechanisms underlying HSF-meditated thermotolerance in maize remain largely unexplored.In this study,we demonstrate that the alternative splicing of ZmHsf23 modulates heat stress tolerance in maize.Hsf23 produced two functional transcripts,Hsf23L and Hsf23S,which differ by the presence of a cryptic mini-exon in Hsf23L that is spliced out in Hsf23S.Both transcripts were strongly induced by heat stress.Mutants lacking Hsf23L alone(hsf23l)or both Hsf23L and Hsf23S(hsf23l23s)exhibited increased susceptibility to heat stress,whereas overexpression of Hsf23S enhanced heat stress tolerance in maize.Subsequently,we found that Hsf23S positively regulates heat stress tolerance by directly activating the transcription of three sHSP genes(Hsp16.9,Hsp17.2,and Hsp18a)and TIL1 gene.In addition,Hsf23L physically interacted with Hsf23S and enhanced the transcriptional activation of Hsf23S on the sHSPs and TIL1 promoters.Notably,genetic analysis suggested that co-overexpression of Hsf23L and Hsf23S further improves heat tolerance of the transgenic plants.Taken together,these results reveal two splicing variants of ZmHsf23 cooperatively regulate maize heat tolerance,thus highlighting potential value of ZmHsf23 in breeding heat-tolerant maize varieties.
基金funded by Guizhou Province Science and Technology Plan Project Qiankehe Foundation-ZK[2023]General 360,362Science and Technology Fund project of Guizhou Provincial Health Commission(gzwkj-2022-09,gzwkj-2023-035)+1 种基金National Natural Science Foundation Cultivation Project of Guizhou Medical University(21NSFCP14,gyfynsfc-2022-25)The PhD Scientific Research Launch Fund Project of the Affiliated Hospital of Guizhou Medical University(gyfybsky-2022-02).
文摘Background:Glioblastoma(GBM)is one of the most malignant types of central nervous system tumors.Oxygen deprivation in the tumor microenvironment is thought to be an important factor in promoting GBM progression.However,the mechanisms of hypoxia-promoted tumor progression remain elusive.Methods:Alternative splicing of diacylglycerol kinase gamma(DGKG)-Δexon13 was amplified and verified by PCR-Sanger sequencing.The functions of DGKG and DGKG-Δexon13 were analyzed by Cell counting kit-8(CCK-8),Transwell,Matrigeltranswell experiments,and in vivo orthotropic GBM animal models.Transcriptome analyses were done to find out the regulated genes.Results:In this study,we found that a new transcript DGKG-Δexon13 was generated in GBM under hypoxia via alternative splicing.Moreover,the results of CCK-8,Transwell,and Matrigel-transwell experiments showed that the proliferation,migration,and invasion abilities of U87-MG and T98G were decreased after DGKG knockdown.Compared to wild-type DGKG,DGKG-Δexon13 overexpression significantly promoted cellular proliferation,migration,and invasion abilities in GBM.Furthermore,in vivo,orthotropic GBM animal models analysis showed that the tumor volumes were much smaller in the DGKG knockdown group.However,the tumor sizes in the DGKG and DGKG-Δexon13 rescue groups were restored,especially in the DGKG-Δexon13 group.Transcriptome analysis revealed that MORC1,KLHDC7B,ATP1A2,INHBE,TMEM119,and FGD3 were altered significantly when DGKG was knocked down.IL-16,CCN2,and EFNB3 were specifically regulated by DGKG-Δexon13.Conclusions:Our study found that hypoxia-induced alternative splicing transcript DGKG-Δexon13 promotes GBM proliferation and infiltration,which might provide a new potential target for the clinical treatment and diagnosis of GBM.
基金supported by the Major Program of National Agricultural Science and Technology of China(NK20220607)the Sichuan Science and Technology Program,China(2023YFH0041)。
文摘Starch biosynthesis is a complex process that relies on the coordinated action of multiple enzymes.Resistant starch is not digested in the small intestine,thus preventing a rapid rise in the glycemic index.Starch synthase 2a(SS2a)is a key enzyme in amylopectin biosynthesis that has significant effects on starch structure and properties.In this study,we identified an ss2a null mutant(M3-1413)with a single base mutation from an ethyl methane sulfonate(EMS)-mutagenized population of barley.The mutation was located at the 3'end of the first intron of the RNA splicing receptor(AG)site,and resulted in abnormal RNA splicing and two abnormal transcripts of ss2a,which caused the inactivation of the SS2a gene.The starch structure and properties were significantly altered in the mutant,with M3-1413 containing lower total starch and higher amylose and resistant starch levels.This study sheds light on the effect of barley ss2a null mutations on starch properties and will help to guide new applications of barley starch in the development of nutritious food products.
基金supported by the National Natural Science Founda-tion of China(82370417,82330011,and U21A20339)the Science Fund for Distinguished Young Scholars of Heilongjiang Province(JQ2024H001)the Heilongjiang Provincial Postdoctoral Science Foundation(LBH-Z23212).
文摘Myocardial infarction(MI)is characterized by focal necrosis resulting from prolonged myocardial ischemia due to coronary artery obstruction.Vascular reconstruction following MI is crucial for improving cardiac function and preventing recurrent infarction.This study investigates the interaction between macrophages and endothelial cells in angiogenesis mediated by nicotinamide mononucleotide(NMN)-induced secretion of macrophage-derived exosomes.We focus on the role of U2 small nuclear RNA auxiliary factor 1(U2af1)gene,a member of the splicing factor serine and arginine(SR)gene family,in the regulation of angiogenesis.Through cardiac ultrasound,Masson staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,Microfil vascular perfusion,and platelet and endothelial cell adhesion molecule 1(CD31)immunofluorescence staining,extracellular vesicles from NMN-stimulated macrophages were shown to exert a protective effect in MI,with proteomic analysis identifying U2AF1 as a candidate protein involved in MI protection.Plasma U2AF1 levels were measured in 70 MI patients,revealing significantly lower levels in individuals with poor coronary collateral vessel(CCV;Rentrop scores 0–1)than in those with good CCV(Rentrop scores 2–3).In both myocardial and hindlimb ischemia mouse models,overexpression of endothelial cell-specific adenoviral overexpression U2AF1 promoted angiogenesis in the heart and hindlimbs and improved cardiac function after MI.Mechanistic studies demonstrated that U2AF1 regulates the alternative splicing(AS)of Yes1-associated transcriptional regulator(Yap1)gene,influencing post-MI angiogenesis and cardiac function recovery.Collectively,our clinical findings suggest that U2AF1 may serve as a therapeutic target for coronary collateral angiogenesis following MI.Given the low immunogenicity and high biosafety of exosomes,this study provides a foundational basis and translational potential for exosome-based therapies in MI treatment.
基金supported by the National Basic Research Program of China (973 Program) (No 2006CB943601)the National Natural Science Foundation of China (NSFC) (No 90919042)
文摘OCT4 is one of the key transcription factors in maintaining the pluripotency and self-renewal of embryonic stem （ES） cells.Human OCT4 can generate two isoforms OCT4A and OCT4B by alternative splicing.OCT4B1 is a recently discovered novel OCT4 spliced variant,which has been considered as a putative marker of stemness.Compared with the OCT4B mRNA,OCT4B1 mRNA is generated by retaining intron 2 as a cryptic exon which contains a TGA stop codon in it.As a result,the protein product of OCT4B1 mRNA could be truncated.Interestingly,we present here that OCT4B1 can indirectly produce the same protein products as OCT4B.We have demonstrated that OCT4B1 mRNA can be spliced into OCT4B mRNA,and encode three protein isoforms.The splicing of OCT4B1 mRNA into OCT4B mRNA can be remarkably inhibited by the mutation of the classical splicing site.Our result suggests that OCT4B mRNA may originate from OCT4B1 mRNA by alternative splicing.
文摘The shaping form of an untwisted yarn-end for the air splicer is analyzed and then a cosine curve form which will have practically good splicing effect is proposed. The yarn motion in the splicing nozzle by applying hydrodynamics and the splicing principle of the air splicer are also studied.
基金supported by the Medical Research Project of Jiangsu Commission of Health(Grant No.M2022015).
文摘The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.
基金supported by the National Natural Science Foundation of China (32060064/32260498)the Guizhou Provincial Excellent Young Talents Project of Science and Technology (Qiankehepingtairencai-YQK (2023)002)+6 种基金the Guizhou Provincial Science and Technology Projects (Qiankehejichu-ZK (2021)General 128Qiankehejichu-ZK (2022)Key 008Qiankehechengguo (2024)General 116Qiankehepingtairencai-BQW (2024)001,qiankehepingtai-YWZ (2024)004)the Key Laboratory of Molecular Breeding for Grain and Oil Crops in Guizhou Province (Qiankehezhongyindi (2023)008)the Key Laboratory of Functional Agriculture of Guizhou Provincial Department of Education (Qianjiaoji (2023)007)the Qiandongnan Science and Technology Support Project (Qiandongnan Kehe Support (2023)06).
文摘Amino acids are the primary form of nitrogen utilization in higher plants,mainly transported by amino acid transporters.In this study,we analyzed the natural variation of amino acid transporter-like 4(OsATL4)in rice germplasm resources,identified its spatiotemporal expression characteristics,determined its substrate transport,and validated its function using transgenic plants.We found that the promoter sequence of OsATL4 varied across 498 rice varieties.The expression level of OsATL4 was higher in japonica rice,which was negatively correlated with tiller number and grain yield.OsATL4 was highly expressed in the basal part,leaf sheath,stem,and young panicle,with its two splicing variants localized to the cell membrane.OsATL4a(the long splicing variant)had a high affinity for transporting Ser,Leu,Phe,and Thr,while OsATL4b(the short splicing variant)had a high affinity for transporting Ser,Leu,and Phe.Blocking OsATL4 promoted axillary bud outgrowth,rice tillering,and grain yield,whereas overexpression lines exhibited the opposite phenotype.Exogenous application of low concentrations of Ser promoted axillary bud outgrowth in overexpression lines,while high concentrations of Ser inhibited it.Conversely,the mutant lines showed the opposite response.Altered expression of OsATL4 might affect the expression of genes in nitrogen,auxin,and cytokinin pathways.We propose that two splicing variants of OsATL4 negatively regulate rice tillering and yield by mediating the transport of amino acids,making it a significant target for high-yield rice breeding.
基金Supported by the National Natural Science Foundation of China,No.82002068,No.82272281the Natural Science Foundation of Guangdong Province,No.2021A1515010949.
文摘Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.
文摘RNA splicing normally generates stable splice- junction sequences in viruses that are important in the context of virus mimicry. Potential variability in envelop proteins may occur with point-mutations inducing cryptic splice-junctions, which would remain unrecognized by T-memory cells of higher organisms in vaccine trials. Such aberrant splice- junctions result from evolution-specific non-conser- vation of actual splice-junction sites due to mutations;as such, locations of splice-junctions in a test DNA sequence could only be imprecisely specified. Such impreciseness of splice-junction locations (or cryptic sites) in a sequence is evaluated in this study via “noisy” attributes (with associated stochastics) to the mutated subspace;and, relevant fuzzy considerations are invoked with membership attributes expressed in terms of a spatial signal-to-noise ratio (SSNR). That is, SSNR adopted as a membership function expresses the belongingness of a site-region to exon/intron subspaces. An illustrative example with actual (Dengue 1 viral) DNA data is furnished demonstrating the pursuit developed in predicting aberrant splice-junctions at cryptic sites in the test sequence.
文摘The growing prevalence of fake images on the Internet and social media makes image integrity verification a crucial research topic.One of the most popular methods for manipulating digital images is image splicing,which involves copying a specific area from one image and pasting it into another.Attempts were made to mitigate the effects of image splicing,which continues to be a significant research challenge.This study proposes a new splicing detectionmodel,combining Sonine functions-derived convex-based features and deep features.Two stages make up the proposed method.The first step entails feature extraction,then classification using the“support vector machine”(SVM)to differentiate authentic and spliced images.The proposed Sonine functions-based feature extraction model reveals the spliced texture details by extracting some clues about the probability of image pixels.The proposed model achieved an accuracy of 98.93% when tested with the CASIA V2.0 dataset“Chinese Academy of Sciences,Institute of Automation”which is a publicly available dataset for forgery classification.The experimental results show that,for image splicing forgery detection,the proposed Sonine functions-derived convex-based features and deep features outperform state-of-the-art techniques in terms of accuracy,precision,and recall.Overall,the obtained detection accuracy attests to the benefit of using the Sonine functions alongside deep feature representations.Finding the regions or locations where image tampering has taken place is limited by the study.Future research will need to look into advanced image analysis techniques that can offer a higher degree of accuracy in identifying and localizing tampering regions.
基金supported by the National Natural Science Foundation of China (Grant Nos.31972411,31722048,and 31630068)the Central Public-interest Scientific Institution Basal Research Fund (Grant No.Y2022PT23)+1 种基金the Innovation Program of the Chinese Academy of Agricultural Sciences,and the Key Laboratory of Biology and Genetic Improvement of Horticultural Crops,Ministry of Agriculture and Rural Affairs,P.R.Chinasupported by NIFA,the Department of Agriculture,via UC-Berkeley,USA。
文摘Brassica oleracea has been developed into many important crops,including cabbage,kale,cauliflower,broccoli and so on.The genome and gene annotation of cabbage(cultivar JZS),a representative morphotype of B.oleracea,has been widely used as a common reference in biological research.Although its genome assembly has been updated twice,the current gene annotation still lacks information on untranslated regions(UTRs)and alternative splicing(AS).Here,we constructed a high-quality gene annotation(JZSv3)using a full-length transcriptome acquired by nanopore sequencing,yielding a total of 59452 genes and 75684 transcripts.Additionally,we re-analyzed the previously reported transcriptome data related to the development of different tissues and cold response using JZSv3 as a reference,and found that 3843 out of 11908 differentially expressed genes(DEGs)underwent AS during the development of different tissues and 309 out of 903 cold-related genes underwent AS in response to cold stress.Meanwhile,we also identified many AS genes,including BolLHCB5 and BolHSP70,that displayed distinct expression patterns within variant transcripts of the same gene,highlighting the importance of JZSv3 as a pivotal reference for AS analysis.Overall,JZSv3 provides a valuable resource for exploring gene function,especially for obtaining a deeper understanding of AS regulation mechanisms.
