Biology subjects

Wu, J.

Publications and source records attributed to Wu, J..

At least 847 records · Page 47Linked to original sources

bioRxiv2019

Capsidiol, a defensive sesquiterpene produced by wild tobacco in response to attack from the fungal pathogen Alternaria alternata, is regulated by an ERF2-like transcription factor

Capsidiol is a sesquiterpenoid phytoalexin produced in Nicotiana and Capsicum species in response to pathogen attack. Whether capsidiol plays a defensive role and how its biosynthesis is regulated in the wild tobacco Nicotiana attenuata when the plant is attacked by Alternaria alternata (tobacco pathotype), a notorious necrotrophic fungus causing brown spot disease, is unknown. Transcriptome analysis indicated that a metabolic switch to sesquiterpene biosynthesis occurred in young leaves of N. attenuata after A. alternata inoculation: many genes leading to sesquiterpene production were strongly up-regulated, including the capsidiol biosynthetic genes, 5-epi-aristolochene synthase (EAS) and 5-epi-aristolochene hydroxylase (EAH). Consistently, the level of capsidiol was increased dramatically in young leaves after fungal inoculation, from not detectable in mock control to 50.68 {+/-} 3.10 {micro}g/g fresh leaves at 3 days post inoculation. Capsidiol-reduced or capsidiol-depleted plants, which were generated by silencing EAHs or EASs by virus-induced gene silencing, were more susceptible to the fungus. In addition, this sesquiterpene exhibited strong anti-fungal activities against A. alternata in vitro when purified from infected plants and applied to fungal growth. Furthermore, an ERF2-like transcription factor was found to positively regulate capsidiol production and plant resistance through the direct transactivation of a capsidiol biosynthetic gene EAS12. Taken together, our results demonstrate that capsidiol, a phytoalexin highly accumulated in N. attenuata plants in response to A. alternata infection, plays an important role in pathogen resistance independent of JA and ethylene signaling pathways, and its biosynthesis is transcriptionally regulated by an ERF2-like transcription factor.\n\nHighlightOur results demonstrate that capsidiol, a phytoalexin highly accumulated in Nicotiana attenuata plants in response to Alternaria alternata attack, plays an important role in pathogen resistance, and its biosynthesis is transcriptionally regulated by an ERF2-like transcription factor.

plant biology↗

bioRxiv2019

Cancer gene therapy by NF-κB-activated cancer cell-specific expression of CRISPR/Cas9 targeting to telomere

NF-{kappa}B has been a luring target for cancer therapy due to its over activation in all tumors. In this study, we showed that a gene therapy named as NF-{kappa}B-activated gene expression (Nage) could be used to induce cancer cell death in vitro and in vivo by utilizing the NF-{kappa}B activity in cancer cells; however, it had no effect on normal cells. In this gene therapy, we constructed a NF-{kappa}B-specific promoter by fusing a NF-{kappa}B decoy sequence to a minimal promoter, which could be bound by the intracellular over activated NF-{kappa}B and thus activate the expression of downstream effector gene in a NF-{kappa}B-specific manner. In this study, we firstly demonstrated the cancer cell-specific activation of NF-{kappa}B. We then demonstrated the cancer cell specificity of Nage vector expression by introducing a Nage vector that could express a reporter gene ZsGreen in various cell lines. We next demonstrated that a Nage vector that could express CRISPR/Cas9 protein and a telomere-targeting sgRNA could be used to specifically induce death of cancer cells. We finally showed that the Cas9/sgRNA Nage vector packaged into the adeno-associated virus (AAV) could be used to inhibit the growth of xenografted tumors in mouse by intravenously injecting recombinant AAV.

cancer biology↗

bioRxiv2019

Kilohertz in vivo imaging of neural activity

Understanding information processing in the brain requires us to monitor neural activity in vivo at high spatiotemporal resolution. Using an ultrafast two-photon fluorescence microscope (2PFM) empowered by all-optical laser scanning, we imaged neural activity in vivo at up to 3,000 frames per second and submicron spatial resolution. This ultrafast imaging method enabled monitoring of both supra- and sub-threshold electrical activity down to 345 m below the brain surface in head fixed awake mice.

neuroscience↗

bioRxiv2019

Primary Studies on the Effect of Microbially Coalbed Methane Enhancement in Suit in the Qinshui Basin

Methods used to yield bio-methane with coal to increase coalbed methane reserves had researched, thus providing a means for improving gas drainage efficiency. One such method utilized to convert coal into gas involves coal biodegradation technology. In order to confirm the practical application of this technology, the experiments were conducted in wells, Z-159, Z-163, Z-167, and Z-7H, in the Qinshui Basin in China, and the duration of the experiments was 32 months. Cl- ion tracer, number changes of Methanogen sp., and coal bed biome evolution indicated that the culture medium diffused in the Z-159 and Z-7H wells. These wells resumed gas production separately. Gasification of coal lasted 635 and 799 days, and yielded 74817 m3 and 251754 m3 coalbed methane in Z-159 and Z-7H wells, respectively. Results demonstrate that coalbed methane enhancement with biogasification of coal is a potential technical to achieve the productivity improvement of coalbed methane wells.

bioengineering↗

bioRxiv2019

Discovery of a redox-thiol switch regulating cellular energy metabolism

Previously, we reported that increased synthesis of the gas hydrogen sulfide (H2S) during the Integrated Stress Response (ISR) induced proteome-wide cysteine-sulfhydration with the predominant modified pathway being enzymes of cellular energy metabolism (Gao, et al. 2015). Using pancreatic beta cells and quantitative proteomics in this study, we identified a Redox Thiol Switch from S-glutathionylation to S-sulfhydration and we named it, RTSGS. About half of the identified proteins are involved in energy metabolism, and one novel target was the mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) whose catalytic Cys306was targeted by both modifications. The enzymatic activity of PCK2 was inhibited by S-glutathionylation, and this inhibition was largely reversed by S-sulfhydration. S-sulfhydration also reversed the S-glutathionylation-mediated inhibition of glucose flux, indicating a broad metabolic significance. We propose that a Redox Thiol Switch from S-glutathionylation to S-sulfhydration is a key mechanism to fine tune cellular energy metabolism in response to different levels of oxidative stress.

biochemistry↗

bioRxiv2019

Gene activation by a CRISPR-assistant trans enhancer

Gene activation is essential to the basic biological research and biomedicine. Therefore, various gene activators such as activation domain-ZNF, TALE and CRISPR proteins have been developed for this end, in which the CRISPR protein dead Cas9 (dCas9) is now most widely used. However, the current gene activators are still limited by their inefficient gene activation activity. In this study, we developed a new strategy, CRISPR-assistant trans enhancer, for activating gene expression in high efficiency by combining dCas9-VP64/sgRNA with a widely used strong enhancer, the CMV enhancer. In this strategy, a trans CMV enhancer DNA was recruited to target gene by dCas9-VP64/sgRNA via annealing between 3 end of sgRNA and CMV enhancer. The trans enhancer activates gene transcription as the natural looped cis enhancer. The trans enhancer could activate both exogenous reporter gene and variant endogenous genes in various cells, with much higher activation efficiency than the current dCas9 activators.

biochemistry↗

bioRxiv2018

Disruption of IRE1α through its Kinase Domain Attenuates Multiple Myeloma

Multiple myeloma (MM) arises from malignant immunoglobulin-secreting plasma cells and remains an incurable, often lethal disease despite recent therapeutic advances. The unfolded-protein response sensor IRE1 supports protein secretion by deploying a kinase-endoribonuclease module to activate the transcription factor XBP1s. MM cells may coopt the IRE1-XBP1s pathway; however, the validity of IRE1 as a potential MM therapeutic target is controversial. Here we show that genetic disruption of IRE1 or XBP1s, or pharmacologic IRE1 kinase inhibition, attenuated subcutaneous or orthometastatic growth of MM tumors in mice, and augmented efficacy of two well-established frontline antimyeloma agents, bortezomib or lenalidomide. Mechanistically, IRE1 perturbation inhibited expression of key components of the ER-associated degradation machinery, as well as cytokines and chemokines known to promote MM growth. Selective IRE1 kinase inhibition reduced viability of CD138+ plasma cells while sparing CD138- cells from bone marrow of newly diagnosed MM patients or patients whose disease relapsed after 1 - 4 lines of treatment in both US- and EU-based cohorts. IRE1 inhibition preserved survival and glucose-induced insulin secretion by pancreatic microislets. Together, these results establish a strong therapeutic rationale for targeting IRE1 with kinase-based small-molecule inhibitors in MM.\n\nSignificance statementMultiple myeloma (MM) is a lethal malignancy of plasma cells. MM cells have an expanded endoplasmic reticulum (ER) that is constantly under stress due to immunoglobulin hyperproduction. The ER-resident sensor IRE1 mitigates ER stress by expanding the ERs protein-folding capacity while supporting proteasomal degradation of misfolded ER proteins. IRE1 elaborates these functions by deploying its cytoplasmic kinase-RNase module to activate the transcription factor XBP1s. The validity of IRE1 as a potential therapeutic target in MM has been questioned. Using genetic and pharmacologic disruption in vitro and in vivo, we demonstrate that the IRE1-XBP1s pathway plays a critical role in MM growth. We further show that IRE1s kinase domain is an effective and safe potential small-molecule target for MM therapy.

cancer biology↗

bioRxiv2018

Race modifies default mode network connectivity in Alzheimer’s disease

ObjectiveTo determine if resting state functional MRI biomarkers of Alzheimers disease (AD) differ between older African Americans and Caucasians.\n\nMethodsWe analyzed MRI profiles from 78 individuals (31 African Americans, 47 Caucasians) with normal cognition (n=36) or mild cognitive impairment/mild AD dementia (MCI/AD, n=42). We compared AD-associated intra-network functional connectivity of the default mode network (DMN) according to race, and correlated domain-specific cognitive functions with functional connectivity which differed between the racial groups.\n\nResultsWe identified key differences in DMN functional connectivity associated with AD between the races. Whereas MCI/AD was associated with decreased functional connectivity within the midline core DMN subsystem in older Caucasians, MCI/AD was instead associated with increased functional connectivity within the same subsystem of older African Americans. This is despite decreased functional connectivity in the medial temporal lobe DMN subsystem in both races. Memory function was also positively associated with connectivity between the precuneus and the posterior cingulate/inferior parietal lobule within the midline core subsystem, in keeping with a less amnestic-profile in older African Americans with MCI/AD.\n\nConclusionsThese findings provide structural support that race modifies the AD phenotypes downstream from cerebral amyloid deposition, and suggests a rsf-MRI correlate of African Americans less amnestic neuropsychological profile in MCI/AD.

neuroscience↗

bioRxiv2018

Wavelength-encoded laser particles for massively-multiplexed cell tagging

Large-scale single-cell analyses have become increasingly important given the role of cellular heterogeneity in complex biological systems. However, no current techniques enable optical imaging of uniquely-tagged individual cells. Fluorescence-based approaches can only distinguish a handful of distinct cells or cell groups at a time because of spectral crosstalk between conventional fluorophores. Here we show a novel class of imaging probes emitting coherent laser light, called laser particles. Made of silica-coated semiconductor microcavities, these laser particles have single-mode emission over a broad range from 1170 to 1580 nm with sub-nm linewidths, enabling massive spectral multiplexing. We demonstrate the stability and biocompatibility of these probes in vitro and their utility for wavelength-multiplexed cell tagging and imaging. We demonstrate real-time tracking of thousands of individual cells in a 3D tumor model for several days showing different behavioral phenotypes. We expect laser particles will enable new approaches for single-cell analyses.

biophysics↗

bioRxiv2018

The ghr-miR164 and GhNAC100 module participates in cotton plant defence against Verticillium dahliae

Previous reports have shown that many miRNAs were identified at the early induction stage during which Verticillium dahliae localizes at the root surface. In this study, we constructed two sRNA libraries of cotton root responses to this fungus at the later induction stage when the pathogen enters the root vascular tissue. We identified 71 known miRNAs and 378 novel miRNAs from two pathogen-induced sRNAs and the control libraries. Combined with degradome and sRNA sequencing, 178 corresponding miRNA target genes were identified, in which 40 target genes from differentially expressed miRNAs were primarily associated with oxidation-reduction and stress responses. More importantly, we characterized the ghr-miR164-GhNAC100 module in the response of the plant to V dahliae infection. A GUS fusion reporter showed that ghr-miR164 directly cleaved the mRNA of GhNAC100 in the post-transcriptional process. ghr-miR164-silencing increased the resistance of the plant to this fungus, while the knockdown of GhNAC100 elevated the susceptibility of the plant, indicating that ghr-miR164-GhNAC100 modulates plant defence through the post-transcriptional regulation. Our data documented that there are numerous miRNAs at the later induction stage that participate in the plant response to V. dahliae, suggesting that miRNAs play important roles in plant resistance to vascular disease.\n\nHighlightAccording to degradome and sRNA sequencings of cotton root in responses to Verticillium dahliae at the later induction stage, many miRNAs and corresponding targets including ghr-miR164-GhNAC100 module participate plant defence.

molecular biology↗

bioRxiv2018

Network-aware mutation clustering of cancer

The grouping of cancers across tissue boundaries is central to precision oncology, but remains a difficult problem. Here we present EPICC (Experimental Protein Interaction Clustering of Cancer), a novel technique to cluster cancer patients based on DNA mutation profile, that leverages knowledge of protein-protein interactions to reduce noise and amplify biological signal. We applied EPICC to data from The Cancer Genome Atlas (TCGA), and both recapitulated known cancer clusterings, and identified new cross-tissue cancer groups that may indicate novel cancer molecular subtypes. Investigation of EPICC clusters revealed new protein modules which were recurrently mutated across cancers, and indicate new avenues for research into cancer biology. EPICC leveraged the Vodafone DreamLab citizen science platform, and we provide our results as a resource for researchers to investigate the role of protein modules in cancer.

bioinformatics↗

bioRxiv2018

Understanding the Ca2+-dependent Fluorescence Change in Red Genetically Encoded Ca2+ Indicators

Genetically encoded Ca2+ indicators (GECIs) are widely used to illuminate dynamic Ca2+ signaling activity in living cells and tissues. Various fluorescence colors of GECIs are available, including red. Red GECIs are promising because longer wavelengths of light scatter less in tissue, making it possible to image deeper. They are engineered from a circularly permuted red fluorescent protein fused to a Ca2+ sensing domain, calmodulin and a calmodulin-binding peptide. A conformational change in the sensing domain upon binding Ca2+ causes a change in the fluorescence intensity of the fluorescent protein. Three factors could contribute to this change in fluorescence: 1) a shift in the protonation state of the chromophore, 2) a change in fluorescence quantum yield, and 3) a change in the extinction coefficient for one-photon excitation or the two-photon cross section for two-photon excitation. We conducted a systematic study of the photophysical properties of a select cohort of red GECIs in their Ca2+-free and Ca2+-saturated states to determine which factors are most important for the Ca2+-dependent change in fluorescence. In total, we analyzed nine red GECIs, including jRGECO1a, K-GECO1, jRCaMP1a, R-GECO1, R-GECO1.2, CAR-GECO1, O-GECO1, REX-GECO1, and a new variant termed jREX-GECO1. We found that these red GECIs could be separated into three classes that each rely on a particular set of factors. Furthermore, in some cases the magnitude of the change in fluorescence was different depending on one-photon excitation or two-photon excitation by up to a factor of two.

biophysics↗

bioRxiv2018

Expression of a recombinant high affinity IgG Fc receptor by engineered NK cells as a docking platform for therapeutic mAbs to target cancer cells

Anti-tumor mAbs are the most widely used and characterized cancer immunotherapy agents. Despite having a significant impact on some malignancies, most cancer patients respond poorly or develop resistance to this therapy. A known mechanism of action of these therapeutic mAbs is antibody-dependent cell-mediated cytotoxicity (ADCC), which is a primarily effector function of NK cells. CD16A on human NK cells has an exclusive role in binding to tumor-bound IgG antibodies. Though CD16A is a potent activating receptor, it is a low affinity Fc{gamma}R and its cell surface levels can be rapidly downregulated by a proteolytic process involving ADAM17 upon NK cell activation, which are likely to limit the efficacy of tumor-targeting therapeutic mAbs in the tumor environment. We sought to enhance NK cell binding to anti-tumor mAbs by engineering these cells with a recombinant Fc{gamma}R consisting of the extracellular region of CD64, the highest affinity IgG Fc receptor expressed by leukocytes, and the transmembrane and cytoplasmic regions of CD16A. This novel recombinant Fc{gamma}R (CD64/16A) was expressed in the human NK cell line NK92 and in induced pluripotent stem cells from which primary NK cells were derived. CD64/16A also lacked the ADAM17 cleavage region in CD16A and it was not rapidly downregulated in expression following NK cell activation during ADCC. CD64/16A on NK cells facilitated conjugation to antibody-treated tumor cells, ADCC, and cytokine production, demonstrating functional activity by its two components. Unlike NK cells expressing CD16A, CD64/16A captured soluble therapeutic mAbs and the modified NK cells mediated tumor cell killing. Hence, CD64/16A could potentially be used as a docking platform on engineered NK cells for therapeutic mAbs and IgG Fc chimeric proteins, allowing for switchable targeting elements, and a novel cancer cellular therapy.

immunology↗

bioRxiv2018

A familial case of Syndactyly type IV due to a novel duplication of ~222.23 kb covering exons 2-17 of the LMBR1 gene: a case report

Syndactyly is one of the most frequent hereditary limb malformations with clinical and genetical complexity. Autosomal dominant Syndactyly type IV (SD4) is a very rare form of syndactyly, occurring as a result of heterozygous mutation in an SHH regulatory element (ZRS) that resides in intron 5 of the LMBR1 gene on chromosome 7q36.3. The SD4 is characterized by complete cutaneous syndactyly of all fingers, cup-shaped hands due to flexion of the fingers and accompanied by polydactyly. Here, we firstly reported a big Chinese family, manifesting cup-shaped hands consistent with SD4 and intrafamilial heterogeneity in clinical phenotype of tibial and fibulal shortening, triphalangeal thumb-polysyndactyly syndrome (TPTPS). Genetically, we identified a novel duplication of [~]222.23 kb covering exons 2-17 of the LMBR1 gene in this family by next generation sequencing. This case expands our new clinical understanding of SD4 phenotype.

genetics↗

bioRxiv2018

Tenuivirus uses a molecular bridge strategy to overcome insect midgut barriers for virus persistent transmission

Many persistent transmitted plant viruses, including Rice stripe tenuivirus (RSV), cause serious damages to crop productions in China and worldwide. Although many reports have indicated that successful insect-mediated virus transmission depends on proper virus-insect vector interactions, the mechanism(s) controlling interactions between viruses and insect vectors for virus persistent transmission remained poorly understood. In this study, we used RSV and its small brown planthopper (SBPH) vector as a working model to elucidate the molecular mechanism controlling RSV virion entrance into SBPH midgut for persistent transmission. We have now demonstrated that this non-enveloped Tenuivirus uses its non-structural glycoprotein NSvc2 as a helper component to bridge the specific interaction between virion and SBPH midgut cells, leading to overcome SBPH midgut barriers for virus persistent transmission. In the absence of this glycoprotein, purified RSV virion is not capable of entering SBPH midgut cells. In RSV-infected cells, glycoprotein NSvc2 is processed into two mature proteins: an amino-terminal protein NSvc2-N and a carboxyl-terminal protein NSvc2-C. We determined that NSvc2-N interacted with RSV virion and bound directly to midgut lumen surface via its N-glycosylation sites. Upon recognition by midgut cells, the midgut cells underwent endocytosis followed by compartmentalizing RSV virion and NSvc2 into early and then late endosomes. The acidic condition inside the late endosome triggered conformation change of NSvc2-C and caused cell membrane fusion via its highly conserved fusion loop motifs, leading to the release of RSV virion from endosome into cytosol. In summary, our results showed for the first time that a rice Tenuivirus uses a molecular bridge strategy to ensure proper interactions between virus and insect midgut for successful persistent transmission.\n\nAuthor summaryOver 75% of the known plant viruses are insect transmitted. Understanding how plant viruses interacted with their insect vectors during virus transmission is one of the key steps to manage virus diseases worldwide. Both the direct and indirect virus-insect vector interaction models have been proposed for virus non-persistent and semi-persistent transmission. However, the indirect virus-vector interaction mechanism during virus persistent transmission has not been reported previously. In this study, we developed a new reverse genetics technology and demonstrated that the circulative and propagative transmitted Rice stripe tenuivirus utilizes a glycoprotein NSvc2 as a helper component to ensure a specific interaction between Tenuivirus virion and midgut cells of small brown planthopper (SBPH), leading to conquering the midgut barrier of SBPH. This is the first report of a helper component mediated-molecular bridge mechanism for virus persistent transmission. These new findings and our new model on persistent transmission expand our understanding of molecular mechanism(s) controlling virus-insect vector interactions during virus transmission in nature.

pathology↗

bioRxiv2018

PIRD: Pan immune repertoire database

MotivationT and B cell receptors (TCRs and BCRs) play a pivotal role in the adaptive immune system by recognizing an enormous variety of external and internal antigens. Understanding these receptors is critical for exploring the process of immunoreaction and exploiting potential applications in immunotherapy and antibody drug design. Although a large number of samples have had their TCR and BCR repertoires sequenced using high-throughput sequencing in recent years, very few databases have been constructed to store these kinds of data. To resolve this issue, we developed a database.\n\nResultsWe developed a database, the Pan Immune Repertoire Database (PIRD), located in China National GeneBank (CNGBdb), to collect and store annotated TCR and BCR sequencing data, including from Homo sapiens and other species. In addition to data storage, PIRD also provides functions of data visualisation and interactive online analysis. Additionally, a manually curated database of TCRs and BCRs targeting known antigens (TBAdb) was also deposited in PIRD.\n\nAvailability and ImplementationPIRD can be freely accessed at https://db.cngb.org/pird.

immunology↗

bioRxiv2018

Lsm12 mediates Polη deubiquitination to help Saccharomyces cerevisiae resist oxidative stress

In Saccharomyces cerevisiae, the Y-family DNA polymerase {eta} (Pol{eta}) regulates genome stability in response to different forms of environmental stress by translesion DNA synthesis. To elucidate the role of Pol{eta} in oxidative stress-induced DNA damage, we deleted or overexpressed the corresponding gene RAD30, and used transcriptome analysis to screen the potential genes associated with RAD30 to respond to DNA damage. Under 2 mM H2O2, deletion of RAD30 resulted in a 2.2-fold decrease in survival and a 2.8-fold increase in DNA damage, whereas overexpression of RAD30 increased survival and decreased DNA damage by 1.2- and 1.4-fold, respectively, compared with that of the wild-type strain. Transcriptome and phenotypic analysis identified Lsm12 as a main factor involved in oxidative stress-induced DNA damage. Deleting LSM12 caused growth defects while its overexpression enhanced cell growth under 2 mM H2O2. This effect was due to the physical interaction of Lsm12 with the UBZ domain of Pol{eta} to enhance Pol{eta} deubiquitination through Ubp3, and consequently promote Pol{eta} recruitment. Overall, these findings demonstrate that Lsm12 is a novel regulator mediating Pol{eta} deubiquitination to promote its recruitment under oxidative stress. Furthermore, this study provides a potential strategy to maintain the genome stability of industrial strains during fermentation.\n\nIMPORTANCEPol{eta} was shown to be critical for cell growth in the yeast Saccharomyces cerevisiae, and deletion of its corresponding gene RAD30 caused a severe growth defect under exposure to oxidative stress with 2 mM H2O2. Furthermore, we found that Lsm12 physically interacts with Pol{eta} and promotes Pol{eta} deubiquitination and recruitment. Overall, these findings indicate Lsm12 as a novel regulator mediating Pol{eta} deubiquitination that regulates its recruitment in response to DNA damage induced by oxidative stress.

cell biology↗

bioRxiv2018

Skin Lesion Classification Via Combining Deep Learning Features and Clinical Criteria Representations

Skin lesion is a severe disease globally. Early detection of melanoma in dermoscopy images significantly increases the survival rate. However, the accurate recognition of skin lesion is extremely challenging manually visualization. Hence, reliable automatic classification of skin lesions is meaningful to improve pathologists accuracy and efficiency. In this paper, we proposed a two-stage method to combine deep learning features and clinical criteria representations to address skin lesion automated diagnosis task. Stage 1 - feature encoding: Modified deep convolutional neural networks (CNNs, in this paper, we used Dense201 and Res50) were fine-tuned to extract rich image global features. To avoid hair noisy, we developed a lesion segmentation U-Net to mask out the decisive regions and used the masked image as CNNs inputs. In addition, color features, texture features and morphological features were exacted based on clinical criteria; Stage 2 - features fusion: LightGBM was used to select the salient features and model parameters, predicting diagnosis confidence for each category. The proposed deep learning frameworks were evaluated on the ISIC 2018 dataset. Experimental results show the promising accuracies of our frameworks were achieved.

bioinformatics↗