Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing

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.

Alternative splicing of the PECTINESTERASE gene encoding a cell wall-degrading enzyme affects postharvest softening in grape

The firmness of table grape berries is a crucial quality parameter. Despite extensive research on postharvest fruit softening, its precise molecular mechanisms remain elusive. To enhance our comprehension of the underlying molecular factors, we initially identified differentially expressed genes(DEGs) by comparing the transcriptomes of folic acid(FA)-treated and water-treated(CK) berries at different time points. We then analyzed the sequences to detect alternatively spliced(AS) genes associated with postharvest softening. A total of 2,559 DEGs were identified and categorized into four subclusters based on their expression patterns, with subcluster-4 genes exhibiting higher expression in the CK group compared with the FA treatment group. There were 1,045 AS-associated genes specific to FA-treated berries and 1,042 in the CK-treated berries, respectively. Gene Ontology(GO) annotation indicated that the AS-associated genes in CK-treated berries were predominantly enriched in cell wall metabolic processes,particularly cell wall degradation processes. Through a comparison between treatment-associated AS genes and subcluster-4 DEGs, we identified eight genes, including Pectinesterase 2(VvPE2, Vitvi15g00704), which encodes a cell wall-degrading enzyme and was predicted to undergo an A3SS event. The reverse transcription polymerase chain reaction further confirmed the presence of a truncated transcript variant of VvPE2 in the FA-treated berries.Our study provides a comprehensive analysis of AS events in postharvest grape berries using transcriptome sequencing and underscores the pivotal role of VvPE2 during the postharvest storage of grape berries.

Improved genome annotation of Brassica oleracea highlights the importance of alternative splicing

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.

Image Splicing Forgery Detection Using Feature-Based of Sonine Functions and Deep Features

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.

2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-Glucoside modulates CHEK2 and CCND1 alternative splicing to inhibit MCF-7 cells proliferation

Background:In our previous study,we observed a synergistic effect of 2,3,5,4’-Tetrahydroxystilbene-2-O-b-D-glucoside combined with adriamycin to induce apoptosis in MCF-7 breast cancer cells.However,the underlying mechanisms of epigenetic modifications,such as alternative splicing,have not been explored.In this study,we aimed to investigate the mechanism by which THSG inhibits MCF-7 cell proliferation using full-length transcriptome sequencing.Methods:First,cell viability was examined using the methyl thiazolyl tetrazolium method and full-length transcriptome sequencing was performed to identify genes and pathways.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used to identify the principal pathways and targets of THSG.Flow cytometry analysis of cell cycle distribution was performed.Meanwhile,the analysis of alternative splicing and domains of the key proteins was conducted.Quantitative polymerase chain reaction and western blotting were performed for verification.Results:THSG showed significant cytotoxic activity in MCF-7 cells.Full-length transcriptome sequencing revealed differential alternative splicing with 173 upregulated and 263 downregulated genes.Further analysis identified distinct differential expression of genes(CHEK2-211 and CCND1-201)involved in the cell cycle in the THSG-treated group.Subsequently,alternative splicing types of CHEK2(mutually exclusive exon)and CCND1(intron retention).We found that THSG downregulated mRNA expression,as confirmed by quantitative polymerase chain reaction analysis.Interestingly,protein structural analysis revealed that THSG treatment led to the generation of CHK2-211,which was the result of a mutation in the amino acid residues(GLU-150,ASN-151)of the CHEK2 domain(VAL-150,GLY-151).and CyclinD1-201 were obtained when an amino acid(ASP-267)in the domain was lost in CyclinD1.Moreover,molecular docking analysis demonstrated that the domains of key proteins could bind THSG more effectively,with no difference in affinity.Western blotting confirmed that THSG inhibited the expression of CHK2 and CyclinD1.Conclusion:THSG modulated the alternative splicing of CHEK2 and CCND1 by inducing G0/G1 cell cycle arrest,consequently suppressing MCF-7 cell proliferation.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

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.

Analysis of Roadbed Splicing at Hub Interchanges

This article discusses the roadbed splicing for hub interchanges.The article starts with a description of the characteristics of junction roadbed splicing.The application of splicing technology is explained using a subgrade splicing scheme of a project.Roadbed splicing involves stepwise excavation and preparative measures like surface cleaning and backfilling.This article serves to provide a valuable reference for road and bridge construction and improve the quality of China’s road and bridge projects,so as to achieve sustainable development of the road and bridge engineering industry.

Splicing factor proline and glutamine-rich is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in hepatocellular carcinoma

Background:Hepatocellular carcinoma(HCC)is the fourth leading cause of cancer-related deaths globally.Splicing factor proline and glutamine-rich(SFPQ)is a multifunctional protein that controls various biological functions.As a potential therapeutic target and a promising prognostic indicator,the potential effects and processes of SFPQ in HCC require further investigation.Methods:The RNA sequencing data were obtained from the Gene Expression Omnibus,International Cancer Genome Consortium,and The Cancer Genome Atlas databases to analyze SFPQ expression and differentially expressed genes(DEGs).We utilized the LinkedOmics database to identify co-expressed genes.A Venn diagram was constructed to determine the overlapping genes between the DEGs and the co-expressed genes.Functional enrichment analysis was performed on the overlapping genes and DEGs.Furthermore,our study involved functional enrichment analysis,a protein-protein interaction network analysis,and an analysis of immune cell infiltration.The cBioPortal and Tumor Immune Single-cell Hub were utilized to investigate the genetic alterations of SFPQ and the single-cell transcriptome visualization of the tumor microenvironment.A ceRNA network was established with the assistance of the ENCORI website.Finally,we elucidated the clinical significance of SFPQ in HCC by employing Kaplan-Meier survival analysis,univariate and multivariate Cox regression,and prognostic nomogram models.Results:The expression of SFPQ in HCC tissues was significantly elevated compared to normal tissues.GSEA results indicated that increased expression of SFPQ was associated with pathways related to HCC.The ceRNA network,including SFPQ,hsa-miR-101-3p,AC023043.4,AC124798.1,AC145207.5,and GSEC,was constructed with the assistance of ENCORI.High SFPQ expression was related to a poor prognosis in HCC and its subtypes.Univariate and multivariate Cox regression analysis showed that elevated SFPQ expression is an independent predictive factor.Conclusions:The overexpression of SFPQ may serve as a potential prognostic biomarker,indicating a poor prognosis in HCC.

A geraniol synthase regulates plant defense via alternative splicing in tea plants

Geraniol is an important contributor to the pleasant floral scent of tea products and one of the most abundant aroma compounds in tea plants;however,its biosynthesis and physiological function in response to stress in tea plants remain unclear.The proteins encoded by the full-length terpene synthase(CsTPS1)and its alternative splicing isoform(CsTPS1-AS)could catalyze the formation of geraniol when GPP was used as a substrate in vitro,whereas the expression of CsTPS1-AS was only significantly induced by Colletotrichum gloeosporioides and Neopestalotiopsis sp.infection.Silencing of CsTPS1 and CsTPS1-AS resulted in a significant decrease of geraniol content in tea plants.The geraniol content and disease resistance of tea plants were compared when CsTPS1 and CsTPS1-AS were silenced.Down-regulation of the expression of CsTPS1-AS reduced the accumulation of geraniol,and the silenced tea plants exhibited greater susceptibility to pathogen infection than control plants.However,there was no significant difference observed in the geraniol content and pathogen resistance between CsTPS1-silenced plants and control plants in the tea plants infected with two pathogens.Further analysis showed that silencing of CsTPS1-AS led to a decrease in the expression of the defense-related genes PR1 and PR2 and SA pathway-related genes in tea plants,which increased the susceptibility of tea plants to pathogens infections.Both in vitro and in vivo results indicated that CsTPS1 is involved in the regulation of geraniol formation and plant defense via alternative splicing in tea plants.The results of this study provide new insights into geraniol biosynthesis and highlight the role of monoterpene synthases in modulating plant disease resistance via alternative splicing.

Serine and arginine rich splicing factor 1:a potential target for neuroprotection and other diseases

Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor.This splicing enables mRNA from a single gene to synthesize different proteins,which have different cellular properties and functions and yet arise from the same single gene.A family of splicing factors,Serine-arginine rich proteins,are needed to initiate the assembly and activation of the spliceosome.Serine and arginine rich splicing factor 1,part of the arginine/serine-rich splicing factor protein family,can either activate or inhibit the splicing of mRNAs,depending on the phosphorylation status of the protein and its interaction partners.Considering that serine and arginine rich splicing factor 1 is either an activator or an inhibitor,this protein has been studied widely to identify its various roles in different diseases.Research has found that serine and arginine rich splicing factor 1 is a key target for neuroprotection,showing its promising potential use in therapeutics for neurodegenerative disorders.Furthermore,serine and arginine rich splicing factor 1 might be used to regulate cancer development and autoimmune diseases.In this review,we highlight how serine and arginine rich splicing factor 1 has been studied concerning neuroprotection.In addition,we draw attention to how serine and arginine rich splicing factor 1 is being studied in cancer and immunological disorders,as well as how serine and arginine rich splicing factor 1 acts outside the central or peripheral nervous system.

Comprehensive analysis of the full-length transcripts and alternative splicing involved in clubroot resistance in Chinese cabbage

Chinese cabbage is an economically important Brassica vegetable worldwide, and clubroot, which is caused by the soilborne protist plant pathogen Plasmodiophora brassicae is regarded as a destructive disease to Brassica crops. Previous studies on the gene transcripts related to Chinese cabbage resistance to clubroot mainly employed RNA-seq technology,although it cannot provide accurate transcript assembly and structural information. In this study, PacBio RS II SMRT sequencing was used to generate full-length transcriptomes of mixed roots at 0, 2, 5, 8, 13, and 22 days after P. brassicae infection in the clubroot-resistant line DH40R. Overall, 39 376 high-quality isoforms and 26 270 open reading frames(ORFs) were identified from the SMRT sequencing data. Additionally, 426 annotated long noncoding RNAs(lncRNAs),56 transcription factor(TF) families, 1 883 genes with poly(A) sites and 1 691 alternative splicing(AS) events were identified. Furthermore, 1 201 of the genes had at least one AS event in DH40R. A comparison with RNA-seq data revealed six differentially expressed AS genes(one for disease resistance and five for defensive response) that are potentially involved in P. brassicae resistance. The results of this study provide valuable resources for basic research on clubroot resistance in Chinese cabbage.

OsTHA8 encodes a pentatricopeptide repeat protein required for RNA editing and splicing during rice chloroplast development

In higher plants, the chloroplast is the most important organelle for photosynthesis and for numerous essential metabolic processes in the cell. Although many genes involved in chloroplast development have been identified, the mechanisms underlying such development are not fully understood. In this study, a rice(Oryza sativa) mutant exhibiting pale green color and seedling lethality was isolated from a mutant library. The mutated gene was identified as an ortholog of THA8(thylakoid assembly 8) in Arabidopsis and maize. This gene is designated as OsTHA8 hereafter. OsTHA8 showed a typical pentatricopeptide repeat(PPR) characteristic of only four PPR motifs. Inactivation of OsTHA8 led to a deficiency in chloroplast development in the rice seedling stage. OsTHA8 was expressed mainly in young leaves and leaf sheaths.The OsTHA8 protein was localized to the chloroplast. Loss of function of OsTHA8 weakened the editing efficiency of ndhB-611/737 and rps8-182 transcripts under normal conditions. Y2H and BiFC indicated that OsTHA8 facilitates RNA editing by forming an editosome with multiple organellar RNA editing factor(OsMORF8) and thioredoxin z(OsTRXz), which function in RNA editing in rice chloroplasts. Defective OsTHA8 impaired chloroplast ribosome assembly and resulted in reduced expression of PEP-dependent genes and photosynthesis-related genes. Abnormal splicing of the chloroplast gene ycf3 was detected in ostha8. These findings reveal a synergistic regulatory mechanism of chloroplast biogenesis mediated by RNA, broaden the function of the PPR family, and shed light on the RNA editing complex in rice.

Transformer 2β regulates the alternative splicing of cell cycle regulatory genes to promote the malignant phenotype of ovarian cancer

Late-stage ovarian cancer(OC)has a poor prognosis and a high metastasis rate,but the underlying molecular mechanism is unclear.RNA binding proteins(RBPs)play important roles in posttranscriptional regulation in the contexts of neoplasia and tumor metastasis.In this study,we explored the molecular functions of a canonical RBP,Transformer 2βhomolog(TRA2B),in cancer cells.TRA2B knockdown in HeLa cells and subsequent wholetranscriptome RNA sequencing(RNA-seq)analysis revealed the TRA2B-regulated alternative splicing(AS)profile.We disrupted TRA2B expression in epithelial OC cells and performed a series of experiments to confirm the resulting effects on OC cell proliferation,apoptosis and invasion.TRA2B-regulated AS was tightly associated with the mitotic cell cycle,apoptosis and several cancer pathways.Moreover,the expression of hundreds of genes was regulated by TRA2B,and these genes were enriched in the functions of cell proliferation,cell adhesion and angiogenesis,which are related to the malignant phenotype of OC.By integrating the alternatively spliced and differentially expressed genes,we found that AS events and gene expression were regulated independently.We then explored and validated the oncogenic functions of TRA2B by knocking down its expression in OC cells.The high TRA2B expression was associated with poor prognosis in patients with OC.In ovarian tissue,TRA2B expression showed a gradual increasing trend with increasing malignancy.We demonstrated the important roles of TRA2B in ovarian neoplasia and aggressive OC behaviors and identified the underlying molecular mechanisms,facilitating the targeted treatment of OC.

A novel pathogenic splicing mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa verified by minigene splicing assay

AIM:To report a novel splicing mutation in the RPGR gene(encoding retinitis pigmentosa GTPase regulator)in a three-generation Chinese family with X-linked retinitis pigmentosa(XLRP).METHODS:Comprehensive ophthalmic examinations including best corrected visual acuity,fundus photography,vision field,and pattern-visual evoked potential were performed to identify the disease phenotype of a six-yearold boy from the family(proband).Genomic DNA was extracted from peripheral blood of five available members of the pedigree.Whole-exome sequencing(WES),Sanger sequencing,and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR.Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants.RESULTS:The proband was diagnosed as having retinitis pigmentosa(RP).He had severe symptoms with early onset.A novel splicing mutation,c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing.Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped,leading to the subsequent deletion of 623 correct amino acids(c.529_619del p.Val177Glnfs*16).CONCLUSION:We identify a novel splice donor site mutation causing aberrant splicing of RPGR.Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.

Exploring Splicing Variants and Novel Genes in Sacred Lotus Based on RNA-seq Data

Sacred lotus(Nelumbo nucifera)is a typical aquatic plant,belonging to basal eudicot plant,which is ideal for genome and genetic evolutionary study.Understanding lotus gene diversity is important for the study of molecular genetics and breeding.In this research,public RNA-seq data and the annotated reference genome were used to identify the genes in lotus.A total of 26,819 consensus and 1,081 novel genes were identified.Meanwhile,a comprehensive analysis of gene alternative splicing events was conducted,and a total of 19,983“internal”alternative splicing(AS)events and 14,070“complete”AS events were detected in 5,878 and 5,881 multi-exon expression genes,respectively.Observations made from the AS events show the predominance of intron retention(IR)subtype of AS events representing 33%.IR is followed by alternative acceptor(AltA),alternative donor(AltD)and exon skipping(ES),highlighting the universality of the intron definition model in plants.In addition,functional annotations of the gene with AS indicated its relationship to a number of biological processes such as cellular process and metabolic process,showing the key role for alternative splicing in influencing the growth and development of lotus.The results contribute to a better understanding of the current gene diversity in lotus,and provide an abundant resource for future functional genome analysis in lotus.

Weber Law Based Approach for Multi-Class Image Forgery Detection

Today’s forensic science introduces a new research area for digital image analysis formultimedia security.So,Image authentication issues have been raised due to the wide use of image manipulation software to obtain an illegitimate benefit or createmisleading publicity by using tempered images.Exiting forgery detectionmethods can classify only one of the most widely used Copy-Move and splicing forgeries.However,an image can contain one or more types of forgeries.This study has proposed a hybridmethod for classifying Copy-Move and splicing images using texture information of images in the spatial domain.Firstly,images are divided into equal blocks to get scale-invariant features.Weber law has been used for getting texture features,and finally,XGBOOST is used to classify both Copy-Move and splicing forgery.The proposed method classified three types of forgeries,i.e.,splicing,Copy-Move,and healthy.Benchmarked(CASIA 2.0,MICCF200)and RCMFD datasets are used for training and testing.On average,the proposed method achieved 97.3% accuracy on benchmarked datasets and 98.3% on RCMFD datasets by applying 10-fold cross-validation,which is far better than existing methods.

GhCTSF1,a short PPR protein with a conserved role in chloroplast development and photosynthesis,participates in intron splicing of rpoC1 and ycf3-2 transcripts in cotton

Cotton is one of the most important textile fibers worldwide.As crucial agronomic traits,leaves play an essential role in the growth,disease resistance,fiber quality,and yield of cotton plants.Pentatricopeptide repeat(PPR)proteins are a large family of nuclear-encoded proteins involved in organellar or nuclear RNA metabolism.Using a virus-induced gene silencing assay,we found that cotton plants displayed variegated yellow leaf phenotypes with decreased chlorophyll content when expression of the PPR gene GhCTSF1 was silenced.GhCTSF1 encodes a chloroplast-localized protein that contains only two PPR motifs.Disruption of GhCTSF1 substantially reduces the splicing efficiency of rpoC1 intron 1 and ycf3 intron 2.Loss of function of the GhCTSF1 ortholog EMB1417 causes splicing defects in rpoC1 and ycf3-2,leading to impaired chloroplast structure and decreased photosynthetic rates in Arabidopsis.We also found that GhCTSF1 interacts with two splicing factors,GhCRS2 and GhWTF1.Defects in GhCRS2 and GhWTF1 severely affect intron splicing of rpoC1 and ycf3-2 in cotton,leading to defects in chloroplast development and a reduction in photosynthesis.Our results suggest that GhCTSF1 is specifically required for splicing rpoC1 and ycf3-2 in cooperation with GhCRS2 and GhWTF1.

RNA m6A dynamic modification mediated by nucleuslocalized FTO is involved in follicular reserve

In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers.The fat-mass and obesity-associated protein(FTO)catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes.Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles,with an inverse relationship observed for m6A levels and nuclear-localized FTO expression.Application of Fto small interfering RNA(si RNA)altered the expression of genes related to cell proliferation,hormone regulation,and cell chemotaxis,and affected RNA alternative splicing.Overexpression of the full-length Fto gene led to changes in m6A levels,alternative splicing of Cdk5,cell proliferation,cell cycle progression,and proportion of primordial follicles.Conversely,overexpression of Fto lacking a nuclear localization signal(NLS)did not significantly alter m6A levels or primordial follicle assembly.These findings suggest that FTO,localized in the nucleus but not in the cytoplasm,regulates RNA m6A demethylation and plays a role in cell proliferation,cell cycle progression,and primordial follicle assembly.These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.

Lightweight Malicious Code Classification Method Based on Improved Squeeze Net

With the growth of the Internet,more and more business is being done online,for example,online offices,online education and so on.While this makes people’s lives more convenient,it also increases the risk of the network being attacked by malicious code.Therefore,it is important to identify malicious codes on computer systems efficiently.However,most of the existing malicious code detection methods have two problems:(1)The ability of the model to extract features is weak,resulting in poor model performance.(2)The large scale of model data leads to difficulties deploying on devices with limited resources.Therefore,this paper proposes a lightweight malicious code identification model Lightweight Malicious Code Classification Method Based on Improved SqueezeNet(LCMISNet).In this paper,the MFire lightweight feature extraction module is constructed by proposing a feature slicing module and a multi-size depthwise separable convolution module.The feature slicing module reduces the number of parameters by grouping features.The multi-size depthwise separable convolution module reduces the number of parameters and enhances the feature extraction capability by replacing the standard convolution with depthwise separable convolution with different convolution kernel sizes.In addition,this paper also proposes a feature splicing module to connect the MFire lightweight feature extraction module based on the feature reuse and constructs the lightweight model LCMISNet.The malicious code recognition accuracy of LCMISNet on the BIG 2015 dataset and the Malimg dataset reaches 98.90% and 99.58%,respectively.It proves that LCMISNet has a powerful malicious code recognition performance.In addition,compared with other network models,LCMISNet has better performance,and a lower number of parameters and computations.

Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway

BACKGROUND Heterogeneous ribonucleoprotein A1(hnRNPA1)has been reported to enhance the Warburg effect and promote colon cancer(CC)cell proliferation,but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.AIM To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.METHODS Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b.The relationship between the expression values and the clinicopathological features of the patients was investigated.Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction,while differences in protein expression were analyzed using western blot.Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays,and cell cycle and apoptosis were detected using flow cytometric assays.The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay.The Warburg effect was evaluated by glucose uptake and lactic acid production assays.RESULTS The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls(P<0.05).Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC,including stage I,II-III,and IV.Furthermore,the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification.HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway,thereby promoting proliferation of HCT116 and SW620 cells.However,the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b,effectively blocking the Warburg effect.CONCLUSION These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.