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1.
Biomed Eng Lett ; 14(2): 187-197, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38374911

RESUMO

Thyroid nodules are common, and patients with potential malignant lesions are usually diagnosed using ultrasound imaging to determine further treatment options. This study aims to propose a computer-aided diagnosis method for benign and malignant classification of thyroid nodules in ultrasound images. We propose a novel multi-task framework that combines the advantages of dense connectivity, Squeeze-and-Excitation (SE) connectivity, and Atrous Spatial Pyramid Pooling (ASPP) layer to enhance feature extraction. The Dense connectivity is used to optimize feature reuse, the SE connectivity to optimize feature weights, the ASPP layer to fuse feature information, and a multi-task learning framework to adjust the attention of the network. We evaluate our model using a 10-fold cross-validation approach based on our established Thyroid dataset. We assess the performance of our method using six average metrics: accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and AUC, which are 93.49, 95.54, 91.52, 91.63, 95.47, and 96.84%, respectively. Our proposed method outperforms other classification networks in all metrics, achieving optimal performance. We propose a multi-task model, DSMA-Net, for distinguishing thyroid nodules in ultrasound images. This method can further enhance the diagnostic ability of doctors for suspected cancer patients and holds promise for clinical applications.

2.
Phys Med Biol ; 69(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38048630

RESUMO

Objective.Low efficiency in medical image segmentation is a common issue that limits computer-aided diagnosis development. Due to the varying positions and sizes of nodules, it is not easy to accurately segment ultrasound images. This study aims to propose a segmentation model that maintains high efficiency while improving accuracy.Approach. We propose a novel layer that integrates the advantages of dense connectivity, dilated convolution, and factorized filters to maintain excellent efficiency while improving accuracy. Dense connectivity optimizes feature reuse, dilated convolution redesigns layers, and factorized convolution improves efficiency. Moreover, we propose a loss function optimization method from a pixel perspective to increase the network's accuracy further.Main results.Experiments on the Thyroid dataset show that our method achieves 81.70% intersection-over-union (IoU), 90.50% true positive rate (TPR), and 0.25% false positive rate (FPR). In terms of accuracy, our method outperforms the state-of-the-art methods, with twice faster inference and nearly 400 times fewer parameters. Meanwhile, in a test on an External Thyroid dataset, our method achieves 77.03% IoU, 82.10% TPR, and 0.16% FPR, demonstrating our proposed model's robustness.Significance.We propose a real-time semantic segmentation architecture for thyroid nodule segmentation in ultrasound images called fully convolution dense dilated network (FCDDN). Our method runs fast with a few parameters and is suitable for medical devices requiring real-time segmentation.


Assuntos
Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Semântica , Ultrassonografia , Diagnóstico por Computador , Processamento de Imagem Assistida por Computador
3.
Pharmaceuticals (Basel) ; 16(6)2023 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-37375784

RESUMO

Sepsis is caused by a dysregulated immune response to infection and is a leading cause of mortality globally. To date, no specific therapeutics are available to treat the underlying septic response. We and others have shown that recombinant human annexin A5 (Anx5) treatment inhibits pro-inflammatory cytokine production and improves survival in rodent sepsis models. During sepsis, activated platelets release microvesicles (MVs) with externalization of phosphatidylserine to which Anx5 binds with high affinity. We hypothesized that recombinant human Anx5 blocks the pro-inflammatory response induced by activated platelets and MVs in vascular endothelial cells under septic conditions via phosphatidylserine binding. Our data show that treatment with wildtype Anx5 reduced the expression of inflammatory cytokines and adhesion molecules induced by lipopolysaccharide (LPS)-activated platelets or MVs in endothelial cells (p < 0.01), which was not observed with Anx5 mutant deficient in phosphatidylserine binding. In addition, wildtype Anx5 treatment, but not Anx5 mutant, improved trans-endothelial electrical resistance (p < 0.05) and reduced monocyte (p < 0.001) and platelet (p < 0.001) adhesion to vascular endothelial cells in septic conditions. In conclusion, recombinant human Anx5 inhibits endothelial inflammation induced by activated platelets and MVs in septic conditions via phosphatidylserine binding, which may contribute to its anti-inflammatory effects in the treatment of sepsis.

4.
Nucleic Acids Res ; 44(10): 4957-67, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-27034468

RESUMO

Benzo[a]pyrene (BP) is a well-known and frequently encountered carcinogen which generates a bulky DNA adduct (+)-trans-10S-BP-N(2)-dG (BP-dG) in cells. DNA polymerase kappa (polκ) is the only known Y-family polymerase that bypasses BP-dG accurately and thus protects cells from genotoxic BP. Here, we report the structures of human polκ in complex with DNA containing either a normal guanine (G) base or a BP-dG adduct at the active site and a correct deoxycytidine. The structures and supporting biochemical data reveal a unique mechanism for accurate replication by translesion synthesis past the major bulky adduct. The active site of polκ opens at the minor groove side of the DNA substrate to accommodate the bulky BP-dG that is attached there. More importantly, polκ stabilizes the lesion DNA substrate in the same active conformation as for regular B-form DNA substrates and the bulky BPDE ring in a 5' end pointing conformation. The BP-dG adducted DNA substrate maintains a Watson-Crick (BP-dG:dC) base pair within the active site, governing correct nucleotide insertion opposite the bulky adduct. In addition, polκ's unique N-clasp domain supports the open conformation of the enzyme and the extended conformation of the single-stranded template to allow bypass of the bulky lesion. This work illustrates the first molecular mechanism for how a bulky major adduct is replicated accurately without strand misalignment and mis-insertion.


Assuntos
Benzopirenos/química , Replicação do DNA , DNA Polimerase Dirigida por DNA/química , Desoxiguanosina/análogos & derivados , Benzopirenos/metabolismo , Sítios de Ligação , Domínio Catalítico , DNA/química , DNA/metabolismo , DNA Polimerase Dirigida por DNA/metabolismo , Desoxiguanosina/química , Desoxiguanosina/metabolismo , Humanos , Conformação de Ácido Nucleico , Ligação Proteica , Domínios Proteicos
5.
Opt Express ; 22(11): 13641-7, 2014 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-24921558

RESUMO

In reverse engineering, reconstruction of 3D point cloud data is the key step to acquire the final profile of the object. However, the quality of 3D reconstruction is influenced by noise in the three-dimensional measurement. This paper aims to tackle the issue of removing the noisy data from the complex point cloud data. The 3D-GPF (Three Dimensional Global Phase Filtering) global phase filtering method is proposed based on the study of phase filtering method, consisting of the steps below. Firstly, the six-step phase shift profilometry is used to obtain the local phase information, and encoding the obtained phase information. Through the global phase unwrapping method, the global phase can be acquired. Secondly, 3D-GPF method is used for the obtained global phase. Finally, the effect of 3D reconstruction is analyzed after the global phase filtering. Experimental results indicate that the noisy points of three-dimensional graphics is reduced 98.02%, the speed of 3D reconstruction is raised 12%.The effect of the proposed global phase filtering method is better than DCT and GSM methods. It is high precision and fast speed, and can be widely used in other 3D reconstruction application.

6.
Mol Microbiol ; 71(3): 678-91, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19054331

RESUMO

DNA polymerases are co-ordinated by sliding clamps (PCNA/beta-clamp) in translesion synthesis. It is unclear how these enzymes assemble on PCNA with geometric and functional compatibility. We report the crystal structure of a full-length Y-family polymerase, Dpo4, in complex with heterodimeric PCNA1-PCNA2 at 2.05 A resolution. Dpo4 exhibits an extended conformation that differs from the Dpo4 structures in apo- or DNA-bound form. Two hinges have been identified in Dpo4, which render the multidomain polymerase flexible conformations and orientations relative to PCNA. Dpo4 binds specifically to PCNA1 on the conserved ligand binding site. The C-terminal peptide of Dpo4 becomes structured with a 3(10) helix and dominates the specific binding. The Y-family polymerase also contacts PCNA1 with its finger, thumb and little finger domains, which are conformation-dependent protein-protein interactions that diversify the binding mode of Dpo4 on PCNA. The structure reveals a molecular model in which substrate/partner binding-coupled multiple conformations of a Y-family polymerase facilitate its recruitment and co-ordination on the sliding clamp. The conformational flexibility would turn the error-prone Y-family polymerase off when more efficient high-fidelity DNA polymerases work on undamaged DNA and turn it onto DNA templates to perform translesion synthesis when replication forks are stalled by DNA lesions.


Assuntos
Proteínas Arqueais/metabolismo , DNA Polimerase beta/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Sulfolobus solfataricus/enzimologia , Proteínas Arqueais/genética , DNA Polimerase beta/genética , Replicação do DNA , Eletroforese em Gel de Poliacrilamida , Ensaio de Desvio de Mobilidade Eletroforética , Modelos Moleculares , Antígeno Nuclear de Célula em Proliferação/genética , Ligação Proteica , Mapeamento de Interação de Proteínas , Estrutura Terciária de Proteína , Sulfolobus solfataricus/genética
7.
Acta Crystallogr D Biol Crystallogr ; 64(Pt 9): 941-9, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18703842

RESUMO

DNA sliding clamps form an oligomeric ring encircling DNA and serve as a moving platform for DNA-processing proteins. The opening and closing of a sliding-clamp ring is essential to load the clamp onto DNA in order to perform its functions. The molecular details of how clamp rings open and enclose DNA are still not clear. Three PCNA homologues have been found in Sulfolobus solfataricus which form a heterotrimer. Taking advantage of their hetero-oligomeric nature, the structures of the PCNAs in monomeric PCNA3, dimeric PCNA1-PCNA2 and trimeric PCNA1-PCNA2-PCNA3 forms were determined at resolutions of 2.6-1.9 A. The distinct oligomeric structures represent different stages in ring formation, which were verified in solution by ultracentrifugation analysis. The heterodimer opens in a V-shape of 130 degrees , while the heterotrimers form a ring with a 120 degrees rotation between monomers. The association of a rigid PCNA3 monomer with an opened PCNA1-PCNA2 heterodimer closes the ring and introduces a spring tension in the PCNA1-PCNA2 interface, thus bending the nine-stranded intermolecular beta-sheet to fit the 120 degrees rotation. The release of the spring tension as PCNA3 dissociates from the ring may facilitate ring opening. The structural features in different assemblies present a molecular model for clamp ring assembly and opening.


Assuntos
Antígeno Nuclear de Célula em Proliferação/química , Subunidades Proteicas/química , Cristalização , Dimerização , Modelos Moleculares , Sulfolobus solfataricus/química , Ultracentrifugação
8.
Proc Natl Acad Sci U S A ; 104(38): 14905-10, 2007 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-17848527

RESUMO

Erroneous replication of lesions in DNA by DNA polymerases leads to elevated mutagenesis. To understand the molecular basis of DNA damage-induced mutagenesis, we have determined the x-ray structures of the Y-family polymerase, Dpo4, in complex with a DNA substrate containing a bulky DNA lesion and incoming nucleotides. The DNA lesion is derived from an environmentally widespread carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BP). The potent carcinogen BP is metabolized to diol epoxides that form covalent adducts with cellular DNA. In the present study, the major BP diol epoxide adduct in DNA, BP-N(2)-deoxyguanosine (BP-dG), was placed at a template-primer junction. Three ternary complexes reveal replication blockage, extension past a mismatched lesion, and a -1 frameshift mutation. In the productive structures, the bulky adduct is flipped/looped out of the DNA helix into a structural gap between the little finger and core domains. Sequestering of the hydrophobic BP adduct in this new substrate-binding site permits the DNA to exhibit normal geometry for primer extension. Extrusion of the lesion by template misalignment allows the base 5' to the adduct to serve as the template, resulting in a -1 frameshift. Subsequent strand realignment produces a mismatched base opposite the lesion. These structural observations, in combination with replication and mutagenesis data, suggest a model in which the additional substrate-binding site stabilizes the extrahelical nucleotide for lesion bypass and generation of base substitutions and -1 frameshift mutations.


Assuntos
Pareamento Incorreto de Bases , Benzopirenos/química , Carcinógenos Ambientais/química , Adutos de DNA/química , DNA Polimerase beta/química , Desoxiguanosina/análogos & derivados , Mutagênese , Pareamento de Bases , Sequência de Bases , Benzo(a)pireno/química , Benzo(a)pireno/metabolismo , Benzo(a)pireno/farmacologia , Benzopirenos/metabolismo , Sítios de Ligação , Carcinógenos Ambientais/metabolismo , Carcinógenos Ambientais/farmacologia , Cristalografia por Raios X , Adutos de DNA/metabolismo , DNA Polimerase beta/genética , DNA Polimerase beta/metabolismo , Primers do DNA/química , Primers do DNA/metabolismo , Desoxiguanosina/química , Desoxiguanosina/metabolismo , Mutação da Fase de Leitura , Modelos Moleculares , Dados de Sequência Molecular , Relação Estrutura-Atividade , Moldes Genéticos
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