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1.
Mol Cell ; 78(3): 382-395.e8, 2020 05 07.
Article in English | MEDLINE | ID: mdl-32183942

ABSTRACT

N6-Methyldeoxyadenosine (6mA) has recently been shown to exist and play regulatory roles in eukaryotic genomic DNA (gDNA). However, the biological functions of 6mA in mammals have yet to be adequately explored, largely due to its low abundance in most mammalian genomes. Here, we report that mammalian mitochondrial DNA (mtDNA) is enriched for 6mA. The level of 6mA in HepG2 mtDNA is at least 1,300-fold higher than that in gDNA under normal growth conditions, corresponding to approximately four 6mA modifications on each mtDNA molecule. METTL4, a putative mammalian methyltransferase, can mediate mtDNA 6mA methylation, which contributes to attenuated mtDNA transcription and a reduced mtDNA copy number. Mechanistically, the presence of 6mA could repress DNA binding and bending by mitochondrial transcription factor (TFAM). Under hypoxia, the 6mA level in mtDNA could be further elevated, suggesting regulatory roles for 6mA in mitochondrial stress response. Our study reveals DNA 6mA as a regulatory mark in mammalian mtDNA.


Subject(s)
DNA, Mitochondrial/metabolism , Deoxyadenosines/metabolism , Methyltransferases/metabolism , Animals , DNA Methylation , DNA, Mitochondrial/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Deoxyadenosines/genetics , Gene Expression Regulation , Hep G2 Cells , Humans , Hypoxia/genetics , Methyltransferases/genetics , Mice, Inbred C57BL , Mitochondria/genetics , Mitochondria/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
2.
Am J Hum Genet ; 111(6): 1061-1083, 2024 06 06.
Article in English | MEDLINE | ID: mdl-38723632

ABSTRACT

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10-8) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10-5). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study.


Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Ovarian Neoplasms , Polymorphism, Single Nucleotide , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Carcinoma, Ovarian Epithelial/genetics , Transcriptome , Risk Factors , Genomics/methods , Case-Control Studies , Multiomics
3.
Nucleic Acids Res ; 52(1): 154-165, 2024 Jan 11.
Article in English | MEDLINE | ID: mdl-37986225

ABSTRACT

Asymmetric cell division (ACD) is a mechanism used by stem cells to maintain the number of progeny. However, the epigenetic mechanisms regulating ACD remain elusive. Here we show that BRD4, a BET domain protein that binds to acetylated histone, is segregated in daughter cells together with H3K56Ac and regulates ACD. ITGB1 is regulated by BRD4 to regulate ACD. A long noncoding RNA (lncRNA), LIBR (LncRNA Inhibiting BRD4), decreases the percentage of stem cells going through ACD through interacting with the BRD4 mRNAs. LIBR inhibits the translation of BRD4 through recruiting a translation repressor, RCK, and inhibiting the binding of BRD4 mRNAs to polysomes. These results identify the epigenetic regulatory modules (BRD4, lncRNA LIBR) that regulate ACD. The regulation of ACD by BRD4 suggests the therapeutic limitation of using BRD4 inhibitors to treat cancer due to the ability of these inhibitors to promote symmetric cell division that may lead to tumor progression and treatment resistance.


Subject(s)
Bromodomain Containing Proteins , Cell Division , Epigenesis, Genetic , RNA, Long Noncoding , Asymmetric Cell Division , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Nuclear Proteins/metabolism , Transcription Factors/metabolism , Bromodomain Containing Proteins/metabolism
4.
Am J Epidemiol ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39191651

ABSTRACT

Common genetic variation throughout the genome together with rare coding variants identified to date explain about a half of the inherited genetic component of epithelial ovarian cancer risk. It is likely that rare variation in the non-coding genome will explain some of the unexplained heritability, but identifying such variants is challenging. The primary problem is lack of statistical power to identifying individual risk variants by association as power is a function of sample size, effect size and allele frequency. Power can be increased by using burden tests which test for association of carriers of any variant in a specified genomic region. This has the effect of increasing the putative effect allele frequency. PAX8 is a transcription factor that plays a critical role in tumour progression, migration and invasion. Furthermore, regulatory elements proximal to target genes of PAX8 are enriched for common ovarian cancer risk variants. We hypothesised that rare variation in PAX8 binding sites are also associated with ovarian cancer risk, but unlikely to be associated with risk of breast, colorectal or endometrial cancer. We have used publicly available, whole-genome sequencing data from the UK 100,000 Genomes Project to evaluate the burden of rare variation in PAX8 binding sites across the genome. Data were available for 522 ovarian cancers, 2,984 breast cancers, 2,696 colorectal cancers, 836 endometrial cancers and 2253 non-cancer controls. Active binding sites were defined using data from multiple PAX8 and H3K27 ChIPseq experiments. We found no association between the burden of rare variation in PAX8 binding sites (defined in several ways) and risk of ovarian, breast or endometrial cancer. An apparent association with colorectal cancer was likely to be a technical artefact as a similar association was also detected for rare variation in random regions of the genome. Despite the null result this study provides a proof-of -principle for using burden testing to identify rare, non-coding germline genetic variation associated with disease. Larger sample sizes available from large-scale sequencing projects together with improved understanding of the function of the non-coding genome will increase the potential of similar studies in the future.

5.
Anal Chem ; 96(35): 14186-14196, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39171919

ABSTRACT

Protein S-sulfhydration involves the regulation of various protein functions, and resolving the S-sulfhydrated proteome (persulfidome) allows for a deeper exploration of various redox regulations. Therefore, we designed a reducible covalent capture method for isolating S-sulfhydrated proteins, which can analyze the persulfidome in biological samples and monitor specific S-sulfhydrated proteins. In this study, we applied this method to reveal the S-sulfhydration levels of proteins, including 3-phosphoglyceraldehyde dehydrogenase, NFκB/p65, and nucleolin. Furthermore, this technique can be used to enrich S-sulfhydrated peptides, aiding in the determination of protein S-sulfhydration modification sites. Finally, we observed that the S-sulfhydration and oxidation of nucleolin on the C543 residue correlate with its nuclear translocation, downstream regulation of p53, Bcl-xL, and Bcl-2 RNA levels and protein expression, as well as the protective function against oxidative stress. Therefore, this method may facilitate the understanding of the regulation of protein function by redox perturbation.


Subject(s)
Nucleolin , Oxidation-Reduction , Phosphoproteins , RNA-Binding Proteins , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/isolation & purification , Phosphoproteins/metabolism , Phosphoproteins/chemistry , Phosphoproteins/analysis , Humans , Proteome/analysis , Proteome/chemistry
6.
Neurol Sci ; 45(6): 2681-2696, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38265536

ABSTRACT

BACKGROUND: Parkinson's disease (PD) ranks as the second most prevalent neurodegenerative disorder globally, and its incidence is rapidly rising. The diagnosis of PD relies on clinical characteristics. Although current treatments aim to alleviate symptoms, they do not effectively halt the disease's progression. Early detection and intervention hold immense importance. This study aimed to establish a new PD diagnostic model. METHODS: Data from a public database were adopted for the construction and validation of a PD diagnostic model with random forest and artificial neural network models. The CIBERSORT platform was applied for the evaluation of immune cell infiltration in PD. Quantitative real-time PCR was performed to verify the accuracy and reliability of the bioinformatics analysis results. RESULTS: Leveraging existing gene expression data from the Gene Expression Omnibus (GEO) database, we sifted through differentially expressed genes (DEGs) in PD and identified 30 crucial genes through a random forest classifier. Furthermore, we successfully designed a novel PD diagnostic model using an artificial neural network and verified its diagnostic efficacy using publicly available datasets. Our research also suggests that mast cells may play a significant role in the onset and progression of PD. CONCLUSION: This work developed a new PD diagnostic model with machine learning techniques and suggested the immune cells as a potential target for PD therapy.


Subject(s)
Neural Networks, Computer , Parkinson Disease , Parkinson Disease/genetics , Parkinson Disease/immunology , Parkinson Disease/diagnosis , Humans , Machine Learning , Transcriptome , Computational Biology , Gene Expression Profiling , Mast Cells/immunology , Random Forest
7.
J Prosthet Dent ; 131(2): 291.e1-291.e9, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38057199

ABSTRACT

STATEMENT OF PROBLEM: The retentive force and deformation of milled polyetheretherketone (PEEK) and polyetherketoneketone (PEKK) removable partial denture (RPD) frameworks are not well understood. PURPOSE: The purpose of this in vitro study was to assess the retentive force and deformation of PEEK and PEKK Akers clasps with different designs and undercut depths. MATERIAL AND METHODS: A master model containing the first and second molar abutments was used to design Akers clasps of different cross-sectional dimensions, undercut depths (0.5 and 0.75 mm), and materials. The components of the removable partial denture framework also included an occlusal rest and were manufactured using a milling machine (n=5). The fatigue resistance of the Akers clasps was measured before and after deformation regarding the retentive forces. RESULTS: The PEEK2-U50 clasp had the largest retentive force with no significant difference among all groups before and after the insertion and removal cycle. In addition, the increased cross-sectional dimensions of the design resulted in significant differences in retentive forces between the PEEK1 and PEEK2 groups and between the PEEK and PEKK materials. CONCLUSIONS: Increasing the clasp's cross-sectional dimensions significantly impacted retentive forces, especially between different PEEK groups and between PEEK and PEKK materials.


Subject(s)
Benzophenones , Chromium Alloys , Denture, Partial, Removable , Polymers , Cross-Sectional Studies , Denture Retention , Polyethylene Glycols , Ketones , Dental Clasps
8.
Molecules ; 29(10)2024 May 19.
Article in English | MEDLINE | ID: mdl-38792256

ABSTRACT

In recent years, dibenzyl disulfide (DBDS) in transformer oils has caused many transformer failures around the world, and its removal has attracted more attention. In this work, nine imidazolium-based ionic liquids (ILs) were applied as effective, green desulfurization extractants for DBDS-containing transformer oil for the first time. The results show that the desulfurization ability of the ILs for DBDS followed the order of [BMIM]FeCl4 > [BMIM]N(CN)2 > [BMIM]SCN > [BMIM](C4H9O)2PO2 > [BMIM]MeSO4 > [BMIM]NTf2 > [BMIM]OTf > [BMIM]PF6 > [BMIM]BF4. Especially, [BMIM]FeCl4 ionic liquid had excellent removal efficiency for DBDS, with its S partition coefficient KN (S) being up to 2642, which was much higher than the other eight imidazolium-based ILs. Moreover, the extractive performance of [BMIM]FeCl4 increased with an increasing molar ratio of FeCl3 to [BMIM]Cl, which was attributed to its Lewis acidity and fluidity. [BMIM]FeCl4 ionic liquid could also avail in the desulfurization of diphenyl sulfide (DPS) from model oils. The experimental results demonstrate that π-π action, π-complexation, and Lewis acid-base interaction played important roles in the desulfurization process. Finally, the ([BMIM]FeCl4) ionic liquid could be recycled five times without a significant decrease in extractive ability.

9.
J Cell Mol Med ; 27(11): 1509-1522, 2023 06.
Article in English | MEDLINE | ID: mdl-37082943

ABSTRACT

Human oral squamous cell carcinoma (OSCC) has been associated with a relatively low survival rate over the years and is characterized by a poor prognosis. C-X3-C motif chemokine ligand 1 (CX3CL1) has been involved in advanced migratory cells. Overexpressed CX3CL1 promotes several cellular responses related to cancer metastasis, including cell movement, migration and invasion in tumour cells. However, CX3CL1 controls the migration ability, and its molecular mechanism in OSCC remains unknown. The present study confirmed that CX3CL1 increased cell movement, migration and invasion. The CX3CL1-induced cell motility is upregulated through intercellular adhesion molecule-1 (ICAM-1) expression in OSCC cells. These effects were significantly suppressed when OSCC cells were pre-treated with CX3CR1 monoclonal antibody (mAb) and small-interfering RNA (siRNA). The CX3CL1-CX3CR1 axis activates promoted PLCß/PKCα/c-Src phosphorylation. Furthermore, CX3CL1 enhanced activator protein-1 (AP-1) activity. The CX3CR1 mAb and PLCß, PKCα, c-Src inhibitors reduced CX3CL1-induced c-Jun phosphorylation, c-Jun translocation into the nucleus and c-Jun binding to the ICAM-1 promoter. The present results reveal that CX3CL1 induces the migration of OSCC cells by promoting ICAM-1 expression through the CX3CR1 and the PLCß/PKCα/c-Src signal pathway, suggesting that CX3CL1-CX3CR1-mediated signalling is correlated with tumour motility and appealed to be a precursor for prognosis in human OSCC.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/pathology , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Protein Kinase C-alpha , Squamous Cell Carcinoma of Head and Neck , Mouth Neoplasms/pathology , Cell Movement , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Cell Line, Tumor , Chemokine CX3CL1/genetics , Chemokine CX3CL1/metabolism
10.
Am J Hum Genet ; 107(4): 622-635, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32946763

ABSTRACT

Quantifying the functional effects of complex disease risk variants can provide insights into mechanisms underlying disease biology. Genome-wide association studies have identified 39 regions associated with risk of epithelial ovarian cancer (EOC). The vast majority of these variants lie in the non-coding genome, where they likely function through interaction with gene regulatory elements. In this study we first estimated the heritability explained by known common low penetrance risk alleles for EOC. The narrow sense heritability (hg2) of EOC overall and high-grade serous ovarian cancer (HGSOCs) were estimated to be 5%-6%. Partitioned SNP heritability across broad functional categories indicated a significant contribution of regulatory elements to EOC heritability. We collated epigenomic profiling data for 77 cell and tissue types from Roadmap Epigenomics and ENCODE, and from H3K27Ac ChIP-seq data generated in 26 ovarian cancer and precursor-related cell and tissue types. We identified significant enrichment of risk single-nucleotide polymorphisms (SNPs) in active regulatory elements marked by H3K27Ac in HGSOCs. To further investigate how risk SNPs in active regulatory elements influence predisposition to ovarian cancer, we used motifbreakR to predict the disruption of transcription factor binding sites. We identified 469 candidate causal risk variants in H3K27Ac peaks that are predicted to significantly break transcription factor (TF) motifs. The most frequently broken motif was REST (p value = 0.0028), which has been reported as both a tumor suppressor and an oncogene. Overall, these systematic functional annotations with epigenomic data improve interpretation of EOC risk variants and shed light on likely cells of origin.


Subject(s)
Carcinoma, Ovarian Epithelial/genetics , Co-Repressor Proteins/genetics , Cystadenocarcinoma, Serous/genetics , Enhancer Elements, Genetic , Histones/genetics , Nerve Tissue Proteins/genetics , Ovarian Neoplasms/genetics , Alleles , Binding Sites , Carcinoma, Ovarian Epithelial/diagnosis , Carcinoma, Ovarian Epithelial/pathology , Chromosome Mapping , Co-Repressor Proteins/metabolism , Cystadenocarcinoma, Serous/diagnosis , Cystadenocarcinoma, Serous/pathology , Female , Genetic Predisposition to Disease , Genome, Human , Genome-Wide Association Study , Histones/metabolism , Humans , Inheritance Patterns , Nerve Tissue Proteins/metabolism , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Penetrance , Polymorphism, Single Nucleotide , Risk
11.
Cancer Cell Int ; 23(1): 266, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37941005

ABSTRACT

BACKGROUND: The hypoxia-responsive long non-coding RNA, RP11-367G18.1, has recently been reported to induce histone 4 lysine 16 acetylation (H4K16Ac) through its variant 2; however, the underlying molecular mechanism remains poorly understood. METHODS: RNA pull-down assay and liquid chromatography-tandem mass spectrometry were performed to identify RP11-367G18.1 variant 2-binding partner. The molecular events were examined utilizing western blot analysis, real-time PCR, luciferase reporter assay, chromatin immunoprecipitation, and chromatin isolation by RNA purification assays. The migration, invasion, soft agar colony formation, and in vivo xenograft experiments were conducted to evaluate the impact of RP11-367G18.1 variant 2-YY1 complex on tumor progression. RESULTS: In this study, RNA sequencing data revealed that hypoxia and RP11-367G18.1 variant 2 co-regulated genes were enriched in tumor-related pathways. YY1 was identified as an RP11-367G18.1 variant 2-binding partner that activates the H4K16Ac mark. YY1 was upregulated under hypoxic conditions and served as a target gene for hypoxia-inducible factor-1α. RP11-367G18.1 variant 2 colocalized with YY1 and H4K16Ac in the nucleus under hypoxic conditions. Head and neck cancer tissues had higher levels of RP11-367G18.1 and YY1 which were associated with poor patient outcomes. RP11-367G18.1 variant 2-YY1 complex contributes to hypoxia-induced epithelial-mesenchymal transition, cell migration, invasion, and tumorigenicity. YY1 regulated hypoxia-induced genes dependent on RP11-367G18.1 variant 2. CONCLUSIONS: RP11-367G18.1 variant 2-YY1 complex mediates the tumor-promoting effects of hypoxia, suggesting that this complex can be targeted as a novel therapeutic strategy for cancer treatment.

12.
Mediators Inflamm ; 2023: 9330439, 2023.
Article in English | MEDLINE | ID: mdl-36643585

ABSTRACT

In this study, we examined the effect of the GP130-targeting molecule, LMT-28, on lipopolysaccharide- (LPS-) induced bone resorption around implants in diabetic models using in vitro and rat animal experiments. First, LMT-28 was added to osteoblasts stimulated by LPS and advanced glycation end products (AGEs), and nuclear factor-κB receptor-activating factor ligand (RANKL) and associated pathways were evaluated. Then, LMT-28 was administered by gavage at 0.23 mg/kg once every 5 days for 2 weeks to type 2 diabetic rats with peri-implantitis induced by LPS injection and silk ligature. The expression of IL-6 and RANKL was evaluated by immunohistochemistry, and the bone resorption around implants was evaluated by microcomputed tomography. The results showed that LMT-28 downregulated the expression of RANKL through the JAK2/STAT3 signaling pathway in osteoblasts stimulated by LPS and AGEs, reduced bone resorption around implants with peri-implantitis, decreased the expression of IL-6 and RANKL, and decreased osteoclast activity in type 2 diabetic rats. This study confirmed the ability of LMT-28 to reduce LPS-induced bone resorption around implants in diabetic rats.


Subject(s)
Bone Resorption , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Peri-Implantitis , Animals , Rats , Bone Resorption/metabolism , Cytokine Receptor gp130 , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/metabolism , Glycation End Products, Advanced/metabolism , Interleukin-6/metabolism , Janus Kinase 2/metabolism , Lipopolysaccharides , Osteoclasts/metabolism , Peri-Implantitis/metabolism , RANK Ligand/metabolism , Signal Transduction , X-Ray Microtomography
13.
Clin Oral Investig ; 27(1): 165-171, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36125622

ABSTRACT

OBJECTIVES: There is insufficient information about the effects of the thickness of externally characterized stains or glazes on CIELAB color parameters and the translucency parameter (TP) of 5 mol% yttria partially stabilized zirconia (5Y-PSZ). The present study evaluated the effect of a thickness reduction of the externally characterized or glazed layer on its CIE2000 color parameters and TP00 of 5Y-PSZ. MATERIALS AND METHODS: Twenty-eight specimens were sectioned from 5Y-PSZ blanks. Three brands of powdered stains (namely VI, SH, and IV) and a glaze (GL) were used to extrinsically stain the specimen surfaces (n = 7 per group). After measuring the final thickness and color, specimens of each group were carefully ground and finally polished. The reduced thickness was carefully controlled in decrements of 0.02 mm on the characterized stains or glazed layers at each reduction cycle until the surface of the un-stained zirconia was exposed. The CIELAB color parameters of specimens were measured using a spectrophotometer. Subsequently, differences in lightness (∆L'), chroma (∆C'), and hue (∆H'), and TP00 values and color differences (ΔE00) were calculated using the CIEDE2000 formula to determine differences between the specimen and the un-stained zirconia at each reduction cycle. A paired-samples t-test, two-way mixed-design analysis of variance, and Pearson correlation coefficient were used to analyze the data (α = 0.05). RESULTS: There were no significant differences in lightness, chroma, hue, or TP00 values before or after glazing or after each reduction cycle of the glazed layer. Mean ΔE00 values ranged between 20.94 and 33.55 after applying the externally characterized stains. With a decreased thickness of the characterized stain layer, there were observed that significant decreases in ∆L', ∆H', ∆C', and ΔE00, and significant increases in TP00. CONCLUSIONS: Increasing the thickness of externally characterized stains decreased the lightness and caused the alternation of chroma and hue, whereas these phenomena were not observed in the glazed group. There was a slight change of CIE2000 color parameters and TP00 when the thickness of the characterized layer exceeded 0.06 mm. CLINICAL RELEVANCE: The application and thickness of externally characterized stains can sensitively affect CIE2000 color parameters and translucency of 5Y-PSZ.


Subject(s)
Coloring Agents , Zirconium , Materials Testing , Staining and Labeling , Surface Properties , Ceramics , Color , Dental Porcelain
14.
Int J Mol Sci ; 24(21)2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37958584

ABSTRACT

LncRNAs are emerging as important regulators of gene expression by controlling transcription in the nucleus and by modulating mRNA translation in the cytoplasm. In this study, we reveal a novel function of lncRNA SNHG15 in mediating breast cancer cell invasion through regulating the local translation of CDH2 mRNA. We show that SNHG15 preferentially localizes at the cellular protrusions or cell leading edge and that this localization is directed by IMP1, a multifunctional protein involved in many aspects of RNA regulation. We demonstrate that SNHG15 also forms a complex with nucleolin, allowing nucleolin to be co-transported with SNHG15 to the cell protrusions, where the accumulated nucleolin is able to bind to CDH2 mRNA. Interaction with nucleolin stabilizes local CDH2 mRNA and regulates its translation, thus promoting cell invasive potential. Our findings reveal an underlying mechanism by which lncRNA could serve as a carrier to transport a protein regulator into a specific cell compartment to enhance target mRNA expression.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Cell Line, Tumor , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Cell Proliferation/genetics , Cell Surface Extensions/metabolism , MicroRNAs/genetics , Gene Expression Regulation, Neoplastic , Nucleolin
15.
BMC Bioinformatics ; 23(1): 318, 2022 Aug 04.
Article in English | MEDLINE | ID: mdl-35927611

ABSTRACT

BACKGROUND: Essential Proteins are demonstrated to exert vital functions on cellular processes and are indispensable for the survival and reproduction of the organism. Traditional centrality methods perform poorly on complex protein-protein interaction (PPI) networks. Machine learning approaches based on high-throughput data lack the exploitation of the temporal and spatial dimensions of biological information. RESULTS: We put forward a deep learning framework to predict essential proteins by integrating features obtained from the PPI network, subcellular localization, and gene expression profiles. In our model, the node2vec method is applied to learn continuous feature representations for proteins in the PPI network, which capture the diversity of connectivity patterns in the network. The concept of depthwise separable convolution is employed on gene expression profiles to extract properties and observe the trends of gene expression over time under different experimental conditions. Subcellular localization information is mapped into a long one-dimensional vector to capture its characteristics. Additionally, we use a sampling method to mitigate the impact of imbalanced learning when training the model. With experiments carried out on the data of Saccharomyces cerevisiae, results show that our model outperforms traditional centrality methods and machine learning methods. Likewise, the comparative experiments have manifested that our process of various biological information is preferable. CONCLUSIONS: Our proposed deep learning framework effectively identifies essential proteins by integrating multiple biological data, proving a broader selection of subcellular localization information significantly improves the results of prediction and depthwise separable convolution implemented on gene expression profiles enhances the performance.


Subject(s)
Deep Learning , Computational Biology/methods , Machine Learning , Protein Interaction Maps , Proteins/metabolism , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism
16.
Genomics ; 113(5): 3083-3091, 2021 09.
Article in English | MEDLINE | ID: mdl-34237377

ABSTRACT

Revealing genomic variation of representative and diverse germplasm is the cornerstone of deploying genomics information into genetic improvement programs of species of agricultural importance. Here we report the re-sequencing of 239 japonica rice elites representing the genetic diversity of japonica germplasm in China, Japan and Korea. A total of 4.8 million SNPs and PAV of 35,634 genes were identified. The elites from Japan and Korea are closely related and relatively less diverse than those from China. A japonica rice pan-genome was constructed, and 35 Mb non-redundant novel sequences were identified, from which 1131 novel genes were predicted. Strong selection signals of genomic regions were detected on most of the chromosomes. The heading date genes Hd1 and Hd3a have been artificially selected during the breeding process. The results from this study lay the foundation for future whole genome sequences-enabled breeding in rice and provide a paradigm for other species.


Subject(s)
Oryza , Alleles , Genetic Variation , Genome, Plant , Oryza/genetics , Plant Breeding , Polymorphism, Single Nucleotide
17.
Clin Oral Investig ; 26(3): 3041-3048, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34845525

ABSTRACT

OBJECTIVES: The effect of toothbrushing on the color, relative translucency, and surface roughness of extrinsically stained zirconia dental restorations is still unclear. The purpose of the present study was to evaluate the optical properties and surface textures of extrinsically stained or glazed partially stabilized zirconia with 5 mol% yttria (5Y-PSZ) after toothbrushing by determining changes in the color, translucency parameter (TP), and surface roughness. MATERIALS AND METHODS: Specimens (2 mm thick; n = 50) were sectioned from 5Y-PSZ blanks. Three brands of powdered stains (namely VI, SH, IV) and a glaze (GL) were used to extrinsically stain the specimen surfaces (n = 10 per group). The specimens were subjected to 10,000-50,000 simulated toothbrushing strokes using a toothpaste slurry (Ora2 PREMIUM Stain clear paste). The color parameters were measured before staining or glazing and before and after simulated brushing. The color changes and TP values can be calculated before and after simulated brushing. The surface roughness was also evaluated. RESULTS: Significant changes were found in the shade and TP values of 5Y-PSZ after extrinsic staining, but no significant changes were found after toothbrushing, irrespective of the staining brand (p > 0.05). The surface roughness of the characterized 5Y-PSZ specimens decreased after toothbrushing, whereas that of the non-characterized 5Y-PSZ group increased. CONCLUSIONS: Toothbrushing markedly affects the surface roughness of extrinsically stained or glazed 5Y-PSZ specimens, whereas no impacts on the color or translucency were observed. CLINICAL RELEVANCE: For esthetic reasons, clinicians and dental technicians prefer to apply extrinsic stains to zirconia restorations, which profoundly affects its appearance. The limited influence of toothbrushing on color and translucency of 5Y-PSZ is promising for clinical applications.


Subject(s)
Esthetics, Dental , Toothbrushing , Ceramics , Dental Porcelain , Materials Testing , Surface Properties , Zirconium
18.
J Prosthet Dent ; 127(1): 115-121, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33234303

ABSTRACT

STATEMENT OF PROBLEM: The effect of heat treatment on the microstructure and mechanical properties of cobalt-chromium (Co-Cr) removable partial denture (RPD) frameworks fabricated by selective laser melting (SLM) is not well understood. PURPOSE: The purpose of this in vitro study was to evaluate the suitability of SLM-fabricated Co-Cr alloys followed by heat treatment as a framework for RPDs by determining the microstructure and mechanical properties. MATERIAL AND METHODS: Dumbbell specimens and RPD frameworks were fabricated by using SLM followed by heat treatment. The effects of the heat treatment on the microstructure were studied by using optical microscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD). Tensile and insertion and removal tests were performed to study the mechanical responses of selective laser melting followed by heat treatment specimens, including the ultimate tensile strength (UTS), 0.2% yield strength (0.2% YS), elongation (E), and retentive forces. Specimens fabricated by using the traditional lost-wax process were used as a control (casting) group. RESULTS: X-ray diffraction indicated that the γ-face-centered cubic phase dominated SLM and selective laser melting followed by heat treatment specimens. Results from optical microscopy and SEM showed microstructural changes under different fabrication and postprocessing heat treatments; it was difficult to observe the grain boundary in the SLM group, whereas submicrometer-scale grains had formed in the selective laser melting followed by heat treatment group. The selective laser melting followed by heat treatment group exhibited the highest elongation and retentive forces compared with the casting and SLM groups. CONCLUSIONS: SLM increased the mechanical properties of Co-Cr alloys. Postprocessing heat treatment further enhanced the tensile ductility. It is suggested that SLM followed by heat treatment is an efficient strategy for fabricating RPD frameworks.


Subject(s)
Denture, Partial, Removable , Chromium , Chromium Alloys , Cobalt , Hot Temperature , Lasers
19.
J Prosthet Dent ; 127(1): 122-127, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33223197

ABSTRACT

STATEMENT OF PROBLEM: Although studies have reported on selective laser melting (SLM)-fabricated removable partial dentures (RPDs), research addressing the trueness of SLM-fabricated RPD metal frameworks is sparse. PURPOSE: The purpose of this in vitro study was to evaluate the trueness of powdered cobalt-chromium (Co-Cr) or titanium-6 aluminum-4 vanadium (Ti-6Al-4V) alloy frameworks for RPDs fabricated by SLM. MATERIAL AND METHODS: A digital scan of a Kennedy class II mandible typodont was obtained to design an RPD framework by using a computer-aided design (CAD) software program (denoted as CRF). Two experimental groups of frameworks were fabricated from the CRF by using SLM in alloys of Co-Cr (SLM-Co-Cr, n=6) and in Ti-6Al-4V (SLM-Ti-6Al-4V, n=6) while a control group was fabricated by using traditional lost-wax casting following stereolithography (CA-Co-Cr, n=6). In total, 18 RPD frameworks were digitally scanned (denoted as CRF), with each scan then superimposed on the CRF and evaluated for discrepancies by using a 3D analysis software program. A nonparametric Kruskal-Wallis test was performed to determine differences in trueness among groups (α=.05). RESULTS: The CA-Co-Cr group showed the highest discrepancy between CEF and CRF. Statistically significant differences were found between the CA-Co-Cr and SLM-fabricated groups (P=.03 for Co-Cr, and P=.016 for Ti-6Al-4V). However, no significant difference was found between the SLM-Co-Cr and SLM-Ti-6Al-4V groups (P=.787). CONCLUSIONS: SLM-fabricated RPD frameworks exhibited higher trueness than CA-Co-Cr fabricated ones, indicating the potential of selective laser melting to produce the geometric shapes required for accurate dental restorations.


Subject(s)
Denture, Partial, Removable , Chromium Alloys , Computer-Aided Design , Dental Alloys , Freezing , Lasers , Titanium
20.
Zhonghua Nan Ke Xue ; 28(2): 167-172, 2022 Feb.
Article in Zh | MEDLINE | ID: mdl-37462491

ABSTRACT

Prostate cancer (PCa) is one of the most common malignancies in aged males, ranking the second in the incidence of malignant tumors in men. Early diagnosis is essential, as advanced PCa is quite difficult to be managed, especially when it becomes castration-resistant or neuroendocrine PCa. Currently, the diagnosis of PCa is often based on pathology by prostate biopsy. Many recent studies focus on the impact of different biopsy methods on the diagnosis of the malignancy, but no consensus has been reached hitherto. This review summarizes various prostate biopsy methods and their latest studies.


Subject(s)
Prostate , Prostatic Neoplasms , Male , Humans , Aged , Prostate/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Biopsy , Prostate-Specific Antigen
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