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1.
Proc Natl Acad Sci U S A ; 121(11): e2312596121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437555

RESUMO

Self-assembled DNA crystals offer a precise chemical platform at the ångström-scale for DNA nanotechnology, holding enormous potential in material separation, catalysis, and DNA data storage. However, accurately controlling the crystallization kinetics of such DNA crystals remains challenging. Herein, we found that atomic-level 5-methylcytosine (5mC) modification can regulate the crystallization kinetics of DNA crystal by tuning the hybridization rates of DNA motifs. We discovered that by manipulating the axial and combination of 5mC modification on the sticky ends of DNA tensegrity triangle motifs, we can obtain a series of DNA crystals with controllable morphological features. Through DNA-PAINT and FRET-labeled DNA strand displacement experiments, we elucidate that atomic-level 5mC modification enhances the affinity constant of DNA hybridization at both the single-molecule and macroscopic scales. This enhancement can be harnessed for kinetic-driven control of the preferential growth direction of DNA crystals. The 5mC modification strategy can overcome the limitations of DNA sequence design imposed by limited nucleobase numbers in various DNA hybridization reactions. This strategy provides a new avenue for the manipulation of DNA crystal structure, valuable for the advancement of DNA and biomacromolecular crystallography.


Assuntos
5-Metilcitosina , DNA , Cristalização , Catálise , Cristalografia
2.
Transfus Apher Sci ; 63(4): 103940, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38781881

RESUMO

Abnormal plasma uric acid (UA) levels, the lipid profile, and plasma proteins in blood are associated with a range of adverse health outcomes. This multicenter, prospective cohort study aimed to determine the possible effects of multiple apheresis plasma donations on plasma UA levels, the lipid profile, and major proteins in plasma donors. Participants were enrolled from 1 April 2021 to 31 August 2022. When their plasma UA (men: >420 µmol/L, women: >360 µmol/L) and/or lipid levels (total cholesterol [TC]: ≥6.2 mmol/L, triglycerides [TGs]: ≥2.3 mmol/L, low-density lipoprotein cholesterol: ≥4.1 mmol/L, or high-density lipoprotein cholesterol [HDL-C]: <1.0 mmol/L) were abnormal at their first plasma donation, the enrolled participants were followed up until they had completed 10 plasma donations. A total of 11485 participants were enrolled, of whom 1861 met the inclusion criteria. During the study period, 320 donors completed 10 plasma donations. None of the participants took any corrective medicine for their abnormal index. The measured parameters were significantly different from the first to the tenth plasma donations (donors with asymptomatic hyperuricemia: UA, P < 0.001; donors with asymptomatic hyperlipidemia: HDL-C, P < 0.001; TC, P = 0.025; TGs, P < 0.001; apolipoprotein B, P = 0.025; all of the plasma donors, immunoglobulin G, P < 0.001). The levels of HDL-C, TC, and apolipoprotein B were increased, and the levels of UA, TGs, and immunoglobulin G were decreased over this time. However, immunoglobulin G levels were still in the normal range. Moreover, the changes in these parameters were closely associated with the frequency of plasma donation during the study period. Repeated apheresis plasma donations can reduce plasma UA and TG levels and increase HDL-C levels; and further evaluation of the clinical significance with a larger sample size is required.

3.
J Am Chem Soc ; 145(8): 4517-4526, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36795970

RESUMO

Chimeric peptide-DNAzyme (CPDzyme) is a novel artificial peroxidase that relies on the covalent assembly of DNA, peptides, and an enzyme cofactor in a single scaffold. An accurate control of the assembly of these different partners allows for the design of the CPDzyme prototype G4-Hemin-KHRRH, found to be >2000-fold more active (in terms of conversion number kcat) than the corresponding but non-covalent G4/Hemin complex and, more importantly, >1.5-fold more active than the corresponding native peroxidase (horseradish peroxidase) when considering a single catalytic center. This unique performance originates in a series of gradual improvements, thanks to an accurate selection and arrangement of the different components of the CPDzyme, in order to benefit from synergistic interactions between them. The optimized prototype G4-Hemin-KHRRH is efficient and robust as it can be used under a wide range of non-physiologically relevant conditions [organic solvents, high temperature (95 °C), and in a wide range of pH (from 2 to 10)], thus compensating for the shortcomings of the natural enzymes. Our approach thus opens broad prospects for the design of ever more efficient artificial enzymes.


Assuntos
DNA Catalítico , Quadruplex G , Peroxidase do Rábano Silvestre/metabolismo , Hemina , Peroxidase/metabolismo , Peroxidases , DNA Catalítico/metabolismo , Peptídeos
4.
Nucleic Acids Res ; 49(16): 9548-9559, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34379785

RESUMO

Genomic sequences susceptible to form G-quadruplexes (G4s) are always flanked by other nucleotides, but G4 formation in vitro is generally studied with short synthetic DNA or RNA oligonucleotides, for which bases adjacent to the G4 core are often omitted. Herein, we systematically studied the effects of flanking nucleotides on structural polymorphism of 371 different oligodeoxynucleotides that adopt intramolecular G4 structures. We found out that the addition of nucleotides favors the formation of a parallel fold, defined as the 'flanking effect' in this work. This 'flanking effect' was more pronounced when nucleotides were added at the 5'-end, and depended on loop arrangement. NMR experiments and molecular dynamics simulations revealed that flanking sequences at the 5'-end abolish a strong syn-specific hydrogen bond commonly found in non-parallel conformations, thus favoring a parallel topology. These analyses pave a new way for more accurate prediction of DNA G4 folding in a physiological context.


Assuntos
Quadruplex G , Nucleotídeos/genética , Oligonucleotídeos/genética , Polimorfismo Genético/genética , Dicroísmo Circular , DNA/genética , DNA/ultraestrutura , Ligação de Hidrogênio , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Nucleotídeos/química , Oligonucleotídeos/química , RNA/genética , RNA/ultraestrutura
5.
J Am Chem Soc ; 144(14): 6311-6320, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35353520

RESUMO

Nanozymes have emerged as a class of novel catalytic nanomaterials that show great potential to substitute natural enzymes in various applications. Nevertheless, spatial organization of multiple subunits in a nanozyme to rationally engineer its catalytic properties remains to be a grand challenge. Here, we report a DNA-based approach to encode the organization of gold nanoparticle clusters (GNCs) for the construction of programmable enzyme equivalents (PEEs). We find that single-stranded (ss-) DNA scaffolds can self-fold into nanostructures with prescribed poly-adenine (polyA) loops and double-stranded stems and that the polyA loops serve as specific sites for seed-free nucleation and growth of GNCs with well-defined particle numbers and interparticle spaces. A spectrum of GNCs, ranging from oligomers with discrete particle numbers (2-4) to polymer-like chains, are in situ synthesized in this manner. The polymeric GNCs with multiple spatially organized nanoparticles as subunits show programmable peroxidase-like catalytic activity that can be tuned by the scaffold size and the inter-polyA spacer length. This study thus opens new routes to the rational design of nanozymes for various biological and biomedical applications.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Catálise , DNA de Cadeia Simples , Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química
6.
J Am Chem Soc ; 143(20): 7792-7807, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-33988990

RESUMO

i-DNA is a four-stranded, pH-sensitive structure formed by cytosine-rich DNA sequences. Previous reports have addressed the conditions for formation of this motif in DNA in vitro and validated its existence in human cells. Unfortunately, these in vitro studies have often been performed under different experimental conditions, making comparisons difficult. To overcome this, we developed a four-dimensional UV melting and annealing (4DUVMA) approach to analyze i-DNA formation under a variety of conditions (e.g., pH, temperature, salt, crowding). Analysis of 25 sequences provided a global understanding of i-DNA formation under disparate conditions, which should ultimately allow the design of accurate prediction tools. For example, we found reliable linear correlations between the midpoint of pH transition and temperature (-0.04 ± 0.003 pH unit per 1.0 °C temperature increment) and between the melting temperature and pH (-23.8 ± 1.1 °C per pH unit increment). In addition, by analyzing the hysteresis between denaturing and renaturing profiles in both pH and thermal transitions, we found that loop length, nature of the C-tracts, pH, temperature, and crowding agents all play roles in i-DNA folding kinetics. Interestingly, our data indicate which conformer is more favorable for the sequences with an odd number of cytosine base pairs. Then the thermal and pH stabilities of "native" i-DNAs from human promoter genes were measured under near physiological conditions (pH 7.0, 37 °C). The 4DUVMA method can become a universal resource to analyze the properties of any i-DNA-prone sequence.


Assuntos
DNA/síntese química , Raios Ultravioleta , DNA/química , Humanos , Concentração de Íons de Hidrogênio , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , Temperatura
7.
Public Health Nurs ; 38(5): 738-750, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33682194

RESUMO

OBJECTIVE: The present study determined the feasibility and initial efficacy of a kindergarten-based, family-involved intervention in improving children's hand hygiene (HH) behaviors. DESIGN: A cluster-randomized controlled trial was performed, with a cluster defined as a kindergarten class. SAMPLE: Participants were recruited from 20 classes in six kindergartens. A total of 289 children and their families were enrolled in the intervention group, and 293 children and their families were enrolled in the control group. MEASUREMENTS: HH behavior and a related knowledge survey, as well as data on absences due to infection, were collected. INTERVENTION: An 8-week training session on HH for children and an education program combining a seminar and WeChat groups for parents were provided to participants in the intervention group. RESULTS: Two HH behaviors of children, namely, HH after playing outside and 7-stage HH compliance, were significantly different between the two groups after the intervention. The two HH behaviors and knowledge of infections of parents/legal guardians in the intervention group were better than those in the control group after the intervention. The number of absences due to infections in children was lower in the intervention group than in the control group. CONCLUSIONS: Kindergarten-based, family-involved interventions effectively improved the HH behavior of kindergarten children and decreased absences due to infections.


Assuntos
Higiene das Mãos , Criança , Humanos , Pais/educação , Instituições Acadêmicas , Inquéritos e Questionários
8.
Angew Chem Int Ed Engl ; 60(18): 10286-10294, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33605024

RESUMO

Recent studies indicate that i-DNA, a four-stranded cytosine-rich DNA also known as the i-motif, is actually formed in vivo; however, a systematic study on sequence effects on stability has been missing. Herein, an unprecedented number of different sequences (271) bearing four runs of 3-6 cytosines with different spacer lengths has been tested. While i-DNA stability is nearly independent on total spacer length, the central spacer plays a special role on stability. Stability also depends on the length of the C-tracts at both acidic and neutral pHs. This study provides a global picture on i-DNA stability thanks to the large size of the introduced data set; it reveals unexpected features and allows to conclude that determinants of i-DNA stability do not mirror those of G-quadruplexes. Our results illustrate the structural roles of loops and C-tracts on i-DNA stability, confirm its formation in cells, and allow establishing rules to predict its stability.

9.
Mikrochim Acta ; 186(12): 786, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31732805

RESUMO

A UV-vis, CD, and differential pulse voltammetric study was performed on the deactivation of the activity of parallel G-quadruplex/hemin DNAzymes (G4 DNAzymes) by Pb(II). The G4 DNAzyme carries a d[TC] sequence at its 3' end and is stabilized by potassium(I). On addition of Pb(II), the K(I) ions in the parallel G4 are replaced by Pb(II) to keep the parallel topology. Intruded Pb(II) decrease the affinity between the topology and hemin, this leads to a decrease of DNAzyme activity for catalyzing the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) by hydrogen peroxide to form a green dye with an absorption maximum at 420 nm. The assay does not use any amplification, and has a linear response in the 0.01 to 10 µM Pb(II) concentration range and a 7.1 nM limit of detection. The method was successfully applied to the analysis of spiked water samples. Graphical abstractSchematic diagram of the colorimetric lead(II) assay based on the competition between K+ and Pb2+ stabilized G-quadruplex/hemin DNAzymes (G4 DNAzymes).


Assuntos
Colorimetria/métodos , DNA Catalítico/química , Hemina/química , Chumbo/análise , Benzotiazóis/química , DNA Catalítico/genética , Quadruplex G , Peróxido de Hidrogênio/química , Indicadores e Reagentes/química , Chumbo/química , Limite de Detecção , Oxirredução , Potássio/química , Ácidos Sulfônicos/química , Poluentes Químicos da Água/análise
10.
J Cell Physiol ; 232(7): 1708-1716, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27404036

RESUMO

DNA methylation has emerged as a crucial regulator of chondrocyte dedifferentiation, which severely compromises the outcome of autologous chondrocyte implantation (ACI) treatment for cartilage defects. However, the full-scale DNA methylation profiling in chondrocyte dedifferentiation remains to be determined. Here, we performed a genome-wide DNA methylation profiling of dedifferentiated chondrocytes in monolayer culture and chondrocytes treated with DNA methylation inhibitor 5-azacytidine (5-AzaC). This research revealed that the general methylation level of CpG was increased while the COL-1A1 promoter methylation level was decreased during the chondrocyte dedifferentiation. 5-AzaC could reduce general methylation levels and reverse the chondrocyte dedifferentiation. Surprisingly, the DNA methylation level of COL-1A1 promoter was increased after 5-AzaC treatment. The COL-1A1 expression level was increased while that of SOX-9 was decreased during the chondrocyte dedifferentiation. 5-AzaC treatment up-regulated the SOX-9 expression while down-regulated the COL-1A1 promoter activity and gene expression. Taken together, these results suggested that differential regulation of the DNA methylation level of cartilage-specific genes might contribute to the chondrocyte dedifferentiation. Thus, the epigenetic manipulation of these genes could be a potential strategy to counteract the chondrocyte dedifferentiation accompanying in vitro propagation. J. Cell. Physiol. 232: 1708-1716, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Diferenciação Celular/genética , Metilação de DNA/genética , Perfilação da Expressão Gênica , Adulto , Azacitidina/farmacologia , Desdiferenciação Celular/efeitos dos fármacos , Desdiferenciação Celular/genética , Diferenciação Celular/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Colágeno Tipo I/metabolismo , Ilhas de CpG/genética , Metilação de DNA/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Feminino , Ontologia Genética , Humanos , Masculino , Fenótipo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição SOX9/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
11.
Chemistry ; 23(17): 4210-4215, 2017 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-28121370

RESUMO

The catalytic activity of G-quadruplex/hemin is much lower than that of proteinous enzymes, so it is very important to increase its activity. Very recently, flanking sequences, which can be regarded as an external part of G-quadruplexes, were found to enhance the activity of G-quadruplex/hemin DNAzyme. However, little is known about the effect of internal parts, such as loop sequences and linkers, on the activity. In the present study, adenine repeats were incorporated into several designed G-quadruplex structures either in the loops, bulges, or linkers, and the constructed G-quadruplex/hemin DNAzyme exhibit about fivefold improvement in peroxidase-mimicking activity in some cases. The enhancement effect may result from the formation of compound I, protoporphyrin⋅FeIV =O.+ , accelerated by dA repeats, which was demonstrated by H2 O2 decay kinetics and pH dependency analysis. The novel enhancement methods described here may help in the development of high-activity DNAzymes, illustrated by a dimer G-quadruplex with flanking adenine at one end, a relatively long adenine run in one loop, and another adenine run in the linker.


Assuntos
Adenina/química , DNA Catalítico/química , Quadruplex G , Hemina/química , Peroxidases/química , Sequência de Bases , Dicroísmo Circular/métodos , Conformação de Ácido Nucleico , Espectrofotometria Ultravioleta/métodos
12.
Saudi Pharm J ; 25(4): 575-579, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28579894

RESUMO

This study was conducted to investigate the effect of magnetic nanoparticle composite scaffold under a pulsed electromagnetic field on bone marrow mesenchymal stem cells (BMSCs), which was achieved by examining the biological behaviors of cell adhesion, proliferation and differentiation on the surface of the scaffolds. This may provide some experimental evidence for the use of magnetic nanoparticles in medical application. The magnetic nanoparticle composite scaffolds were evaluated and characterized by the following indexes: the cell proliferation was detected by the CCK-8 method, the alkaline phosphatase (ALP) activity was examined by a detection kit, and the expression of type I collagen and osteocalcin gene were evaluated by RT-PCR. The CCK-8 test showed that there was no significant difference in Group A (BMSCs-seeded magnetic scaffolds under the electromagnetic field), B (BMSCs-seeded magnetic scaffolds) and C (BMSCs cultured alone) (P > 0.05). The value for the ALP activity in Group A was higher than the other two groups. In addition, the RT-PCR results showed that the expression of type I collagen gene in Group A was enhanced (P < 0.05), suggesting that the magnetic nanoparticles combined with the pulsed electromagnetic field had a positive effect on the osteogenic differentiation of BMSCs. However, the expression of osteocalcin was not significantly different in three groups (P > 0.05). To conclude, magnetic nanoparticles may induce the osteogenic differentiation with the action of the pulsed electromagnetic field.

13.
Angew Chem Int Ed Engl ; 56(52): 16636-16640, 2017 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-29105965

RESUMO

The quadruplex-based DNAzyme system is one of the most useful artificial enzymes or catalysts; their unique properties make them reliable alternatives to proteins for performing catalytic transformation. The first prototype of a thermally stable DNAzyme system is presented. This thermophilic DNAzyme is capable of oxidizing substrates at high temperatures (up to 95 °C) and long reaction times (up to 18 h at 75 °C). The catalytic activity of the DNAzymes were investigated with the standard peroxidase-mimicking oxidation of 2,2'-azino-bis(3-ethylbenzothiozoline-6-sulfonic acid) (ABTS) by H2 O2 . The step-by-step design of this unique heat-activated G-quadruplex/hemin catalyst, including the modification of adenines at both ends of G-tracts, the choice of cation, and its concentration for DNAzyme stabilization, is described. This work investigates thoroughly the molecular basis of these catalytic properties and provides an example of an industrially relevant application.


Assuntos
DNA Catalítico/química , Quadruplex G , Hemina/química , Benzotiazóis/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Catálise , DNA Catalítico/metabolismo , Peróxido de Hidrogênio/química , Azul de Metileno/química , Oxirredução , Peroxidase/metabolismo , Ácidos Sulfônicos/química
14.
J Transl Med ; 12: 88, 2014 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-24708713

RESUMO

Cartilage tissue engineering is arising as a technique for the repair of cartilage lesions in clinical applications. However, fibrocartilage formation weakened the mechanical functions of the articular, which compromises the clinical outcomes. Due to the low proliferation ability, dedifferentiation property and low production of cartilage-specific extracellular matrix (ECM) of the chondrocytes, the cartilage synthesis in vitro has been one of the major limitations for obtaining high-quality engineered cartilage constructs. This review discusses cells, biomaterial scaffolds and stimulating factors that can facilitate the cartilage-specific ECM production and accumulation in the in vitro culture system. Special emphasis has been put on the factors that affect the production of ECM macromolecules such as collagen type II and proteoglycans in the review, aiming at providing new strategies to improve the quality of tissue-engineered cartilage.


Assuntos
Cartilagem Articular/metabolismo , Proteínas da Matriz Extracelular/biossíntese , Engenharia Tecidual , Animais , Terapia Genética , Humanos , Técnicas In Vitro , Alicerces Teciduais
15.
Int J Biol Macromol ; 265(Pt 2): 130697, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38490395

RESUMO

Chemotherapy, the most common class of anticancer drugs, is considerably limited owing to its adverse side effects. In this study, we aimed to evaluate the protective effect and mechanism of action of large-leaf yellow tea polysaccharides (ULYTP-1, 1.29 × 104 Da) against chemotherapeutic 5-fluorouracil (5-Fu). Structural characterisation revealed that ULYTP-1 was a ß-galactopyranouronic acid. Furthermore, ULYTP-1 promoted autolysosome formation, activating autophagy and reducing the oxidative stress and inflammation caused by 5-Fu. Our in vivo study of 4 T1 tumour-bearing mice revealed that ULYTP-1 also attenuated 5-Fu toxicity through modulation of the gut microbiota. Moreover, ULYTP-1 effectively protected immune organs and the liver from 5-Fu toxicity, while promoting its tumour-inhibitory properties. The current findings provide a new strategy for optimising chemotherapy regimens in the clinic.


Assuntos
Fluoruracila , Polissacarídeos , Animais , Camundongos , Linhagem Celular Tumoral , Fluoruracila/uso terapêutico , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Autofagia , Chá
16.
JACS Au ; 4(3): 1125-1133, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38559725

RESUMO

DNA nanostructures serve as precise templates for organizing organic dyes, enabling the creation of programmable artificial photonic systems with efficient light-harvesting and energy transfer capabilities. However, regulating the organization of organic dyes on DNA frameworks remains a great challenge. In this study, we investigated the factors influencing the self-assembly behavior of cyanine dye K21 on DNA frameworks. We observed that K21 exhibited diverse assembly modes, including monomers, H-aggregates, J-aggregates, and excimers, when combined with DNA frameworks. By manipulating conditions such as the ion concentration, dye concentration, and structure of DNA frameworks, we successfully achieved precise control over the assembly modes of K21. Leveraging K21's microenvironment-sensitive fluorescence properties on DNA nanostructures, we successfully discriminated between the chirality and topology structures of physiologically relevant G-quadruplexes. This study provides valuable insights into the factors influencing the dynamic assembly behavior of organic dyes on DNA framework nanostructures, offering new perspectives for constructing functional supramolecular aggregates and identifying DNA secondary structures.

17.
Comput Methods Programs Biomed ; 231: 107380, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36745954

RESUMO

BACKGROUND AND OBJECTIVE: Emotion classification tasks based on electroencephalography (EEG) are an essential part of artificial intelligence, with promising applications in healthcare areas such as autism research and emotion detection in pregnant women. However, the complex data acquisition environment provides a variable number of EEG channels, which interferes with the model to simulate the process of information transfer in the human brain. Therefore, this paper proposes an improved graph convolution model with dynamic channel selection. METHODS: The proposed model combines the advantages of 1D convolution and graph convolution to capture the intra- and inter-channel EEG features, respectively. We add functional connectivity in the graph structure that helps to simulate the relationship between brain regions further. In addition, an adjustable scale of channel selection can be performed based on the attention distribution in the graph structure. RESULTS: We conducted various experiments on the DEAP-Twente, DEAP-Geneva, and SEED datasets and achieved average accuracies of 90.74%, 91%, and 90.22%, respectively, which exceeded most existing models. Meanwhile, with only 20% of the EEG channels retained, the models achieved average accuracies of 82.78%, 84%, and 83.93% on the above three datasets, respectively. CONCLUSIONS: The experimental results show that the proposed model can achieve effective emotion classification in complex dataset environments. Also, the proposed channel selection method is informative for reducing the cost of affective computing.


Assuntos
Inteligência Artificial , Redes Neurais de Computação , Gravidez , Feminino , Humanos , Emoções , Encéfalo , Eletroencefalografia
18.
Thorac Cancer ; 14(18): 1753-1763, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37160413

RESUMO

BACKGROUND: Breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) tumor suppressor genes play crucial roles in DNA repair and regulation of transcription. Mutations in these genes are closely associated with the occurrence of cancers. However, the mutation status of BRCA gene in central south Chinese lung cancer patients remains unclear, and its expression levels in lung cancer also need to be further explored. METHODS: In this study, we use next-generation sequencing (NGS) technology to analyze the BRCA genes mutations in 462 central south Chinese lung cancer patients. Public databases including cBioportal, Catalogue Of Somatic Mutations In Cancer (COSMIC), The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) and Expression Profiling Interactive Analysis (GEPIA) are also applied to explore the expression level and mutation status of BRCA in lung cancer patients and their relationships with the prognosis. RESULTS: We found that the mutation rate of BRCA1/2 in central south Chinese lung cancer patients is 4.3% and 6.5% respectively, and missense mutations account for the majority in both BRCA1/2, which are similar to the international status of BRCA1/2 from public databases. In addition, 45 novel mutations of BRCA1/2 in lung cancer are reported in this study. Furthermore, we find that the BRCA2 mutations are negatively correlated with overall survival rate in lung cancer using cBioportal. Last, we demonstrate that both of the mRNA and protein levels of BRCA1/2 are upregulated in lung cancer, and the elevated mRNA expression levels are positively linked with poor prognosis. CONCLUSION: In general, our study better complements knowledge of the BRCA1/2 mutation status in the Chinese lung cancer patients, and firstly reveals the association between BRCA1/2 expression levels and prognosis of lung cancer patients, which may provide great value for the early diagnosis and clinical treatment of lung cancer.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Humanos , Feminino , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Mutação , Neoplasias Pulmonares/genética , RNA Mensageiro , Predisposição Genética para Doença
19.
J Cancer ; 14(7): 1132-1140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37215453

RESUMO

Objective: An essential component of precision medical treatment for colorectal cancer (CRC) is the use of microsatellite state in combination with polymerase chain reaction (PCR) and immunohistochemistry (IHC) as the primary clinical detection methods. Microsatellite instability-high (MSI-H) or mismatch-repair deficiency (dMMR) accounts for about 15% of all CRC patients. Characterized by a high mutation burden, MSI-H is a predictive biomarker of immune checkpoint inhibitors (ICIs). Misdiagnosis of microsatellite status has been shown to be an important cause of resistance to immune checkpoint inhibitors. Therefore, a rapid and accurate assessment of microsatellite status can be beneficial for precision medicine in CRC. Methods: We evaluated the rate of discordance between PCR and IHC detection of microsatellite status from a cohort of patients that had 855 colorectal cancers. PCR-based microsatellite assay was performed using a set of five monomorphic mononucleotide makers (NR-24, BAT-25, CAT-25, BAT-26, MONO-27) and two polymorphic pentanucleotide (Penta D and Penta E). IHC was used to detect the absence of mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2). The inconsistency rates of the two assays were evaluated. Results: Among 855 patients,15.6% (134 to 855) cases were identified as MSI-H by PCR, whereas 16.9% (145 to 855) cases were identified as dMMR by IHC. There were 45 patients with discordant results between IHC and PCR. Of these, 17 patients were classified as MSI-H/pMMR and 28 patients as MSS/dMMR. When the clinicopathological characteristics of these 45 patients were compared to those of the 855 patients, it was found that more patients were younger than 65 years old (80% to 63%), more were male (73% to 62%), more were located in the right colon (49% to 32%), and more were poorly differentiated (20% to 15%). Conclusion: Our study demonstrated a high concordance between the PCR and IHC results. In order to reduce the ineffective treatment of ICIs due to MSI misdiagnosis, the patient's age, gender, tumor location and degree of differentiation should be included in the clinician's selection of MSI testing in colorectal cancer.

20.
Signal Transduct Target Ther ; 8(1): 48, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36725837

RESUMO

In the treatment of most malignancies, radiotherapy plays a significant role. However, the resistance of cancer cells to ionizing radiation (IR) is the main reason for the failure of radiotherapy, which causes tumor recurrence and metastasis. In this study, we confirmed that GPR162, an orphan receptor in the G-protein-coupled receptor family, acted as a novel radiotherapy sensitizer by interacting with the stimulator of interferon genes (STING), which targeted DNA damage responses, activated IRF3, accelerated the activation of type I interferon system, promoted the expression of chemokines including CXCL10 and CXCL4, and inhibited the occurrence and development of tumors. Interestingly, the activation of STING by overexpression of GPR162 was independent of the classical pathway of cGAS. STING inhibitors could resist the antitumor effect of overexpression of GPR162 in IR-induced mouse models. In addition, most solid tumors showed low expression of GPR162. And the higher expression of GPR162 indicated a better prognosis in patients with lung adenocarcinoma, liver cancer, breast cancer, etc. In summary, these results suggested that GPR162 may serve as a potential sensitizer of radiotherapy by promoting radiotherapy-induced STING-IFN production and increasing the expression of chemokines including CXCL10 and CXCL4 in DNA damage response, providing an alternative strategy for improving cancer radiotherapy.


Assuntos
Interferon Tipo I , Neoplasias , Radiossensibilizantes , Camundongos , Animais , Transdução de Sinais/genética
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