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1.
Heliyon ; 10(9): e30185, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38720748

RESUMO

This paper aims to accurately assess and effectively manage various security risks in the community and overcome the challenges faced by traditional models in handling large amounts of features and high-dimensional data. Hence, this paper utilizes the back propagation neural network (BPNN) to optimize the security risk assessment model. A key challenge of researching community security risk assessment lies in accurately identifying and predicting a range of potential security threats. These threats may encompass natural disasters, public health crises, accidents, and social security issues. The intricate interplay of these risk factors, combined with the dynamic nature of community environments, presents difficulties for traditional risk assessment methodologies to address effectively. Initially, this paper delves into the factors influencing safety incidents within communities and establishes a comprehensive system of safety risk assessment indicators. Leveraging the adaptable and generalizable nature of the BPNN model, the paper proceeds to optimize the BPNN model, enhancing the security risk assessment model through this optimization. Subsequent comparison experiments with traditional models validate the rationality and effectiveness of the proposed model, with hidden layer nodes set at various levels like 10, 15, 20, 25, 30, and 35. These traditional models include Convolutional Neural Network (CNN), Long Short-Term Memory Network (LSTM), Bidirectional Encoder Representations from Transformers (BERT), Generative Pre-trained Transformer (GPT), and eXtreme Gradient Boosting (XGBOOST). Experimental findings demonstrate that with 20 hidden layer nodes, the optimized model achieves a remarkable final recognition accuracy of 99.1 %. Moreover, the optimized model exhibits significantly lower final function loss compared to models with different node numbers. Increasing the number of hidden layer nodes may diminish the optimized model's fit and accuracy. Comparison with traditional models reveals that the average accuracy of the optimized model in community risk identification reaches 98.5 %, with a maximum accuracy of 99.6 %. This marks an improvement of 9%-11 % in recognition accuracy across various risk factors compared to traditional models. Regarding system response time and resource utilization, the optimized model exhibits a response time ranging from 100 ms to 120 ms and consistently lower resource utilization rates across all scenarios, underscoring its efficiency in community security risk assessment. In conclusion, this experiment sheds light on the underlying mechanisms and patterns of community safety risk formation, offering novel perspectives and methodologies for researching community safety risk assessment. The paper concludes by presenting recommendations and strategies for addressing community safety risks based on experimental analysis.

2.
Sci Total Environ ; 903: 166580, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-37633387

RESUMO

The facilitation of microplastics (MPs) on bacterial resistance has attracted wide concern, due to the widespread presence of MPs in environmental media and their ubiquitous contact with bacteria strains. Furthermore, MPs possibly co-exist with antibiotics to trigger combined stress on bacterial survival. Therefore, it is significant to reveal the dose-responses of MPs and MP-antibiotic mixtures on bacterial endogenous and exogenous resistance. In this study, 0.1 and 5 µm polystyrenes with no surface functionalization (PS-NF, no charge), surface functionalized with amino groups (PS-NH2, positive charge) and carboxyl groups (PS-COOH, negative charge) were selected as the test MPs, and norfloxacin (NOR) was set as the representative of antibiotics. It was found that six types of PS all inhibited the growth of Escherichia coli (E. coli) but induced hormetic dose-responses on the mutation frequency (MF) and conjugative transfer frequency (CTF) of RP4 plasmid in E. coli. Moreover, these hormetic effects exhibited size- and surface charge-dependent features, where 0.1 µm PS-NH2 (100 mg/L) triggered the maximum stimulatory rates on MF (363.63 %) and CTF (74.80 %). The hormetic phenomena of MF and CTF were also observed in the treatments of PS-NOR mixtures, which varied with the particle size and surface charge of PS. In addition, the interactive effects between PS and NOR indicated that the co-existence of PS and NOR might trigger greater resistance risk than the single pollutants. Mechanistic exploration demonstrated that the increase of cellular reactive oxygen species and the variation of cell membrane permeability participated in the hormetic effects of PS and PS-NOR mixtures on bacterial resistance. This study provides new insights into the individual effects of MPs and the combined effects of MP-antibiotic mixtures on bacterial resistance, which will promote the development of environmental risk assessment of MPs from the perspective of bacterial resistance.

3.
Molecules ; 28(15)2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37570821

RESUMO

Fragmentation mechanisms of some prazoles and their related substances were newly investigated in this paper via positive mode ESI-TOF HRMS1 and HRMS2. Some novel fragmentation rules or ions were found or detected in the research. The pyridine and the benzoimidazole ring remained in most cases during the ionization, and heterolytic fragmentations often occurred near the -S(O)nCH2- linker to give the [1,3]-H migration ion or [1,7]-H migration ion rearranging across the benzoimdazole ring. Smiles rearrangement ionizations also frequently occurred, initiated by the attack of the lone pair electrons from the pyridine ring, and the sulfones gave special N-(2-benzoimdazolyl) pyridine ions (11b and 12c) by a direct extraction from SO2, and the thioethers gave similar framework ions (8c, 9c and 10c) via the rearrangement and a further homolytic cleavage of SH radicals. However, the sulfoxides were seldom detected in the corresponding Smiles rearrangement ions during our measurement, and the N'-oxides of the pyridines did not undergo the Smiles rearrangement ionization due to the absence of the lone pair electrons. The 5/6-membered chelating ions with Na+ or K+ were frequently detected as the molecular and further fragment ions. Some novel and interesting fragment ions containing bivalent (8b and 9b), tetravalent (4b, 5c and 6c) or hexavalent (15b and 16b) sulfurs were first reported here.

4.
Scand J Psychol ; 64(6): 802-809, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37345676

RESUMO

Social avoidance and distress are the primary aspects of social anxiety. Nonautistic people with high levels of autistic traits are more likely to exhibit social avoidance and distress. However, research has yet to reveal how autistic traits induce social avoidance and distress. To fill this gap, the present study recruited 708 participants to complete the 25-item Autism Spectrum Quotient, Social Avoidance and Distress Scale, Chinese Perceived Stress Scale, and Interpersonal Alienation Subscale. The results indicated that autistic traits significantly predicted social avoidance and distress in nonautistic people. In addition, autistic traits induced social avoidance and distress through perceived stress and interpersonal alienation, respectively. Importantly, perceived stress and interpersonal alienation (including the subdimensions of interpersonal alienation: sense of loneliness, sense of social isolation, and alienation between family members) partially mediated the relationships between autistic traits and social avoidance and distress. Overall, autistic traits predict social avoidance and distress via perceived stress and interpersonal alienation. This finding extends the hypothetical model of clinical anxiety in autism spectrum disorders. Furthermore, reducing perceived stress and interpersonal alienation in nonautistic people with high levels of autistic traits may be a valid intervention method to prevent and eliminate their social avoidance and distress.


Assuntos
Transtorno Autístico , Testes Psicológicos , Humanos , Comportamento Social , Autorrelato , Estresse Psicológico
5.
Nat Commun ; 14(1): 3448, 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37301886

RESUMO

Deep cement mixing piles are a key technology for treating settlement distress of soft soil subgrade. However, it is very challenging to accurately evaluate the quality of pile construction due to the limitations of pile material, large number of piles and small pile spacing. Here, we propose the idea of transforming defect detection of piles into quality evaluation of ground improvement. Geological models of pile group reinforced subgrade are constructed and their ground-penetrating radar response characteristics are revealed. We have also developed ground-penetrating radar attribute analysis technology and established ground-penetrating radar technical system for evaluating the quality of ground improvement. We further prove that the ground-penetrating radar results integrating single-channel waveform, multi-channel section and attributes can effectively detect the defects and stratum structure after ground improvement. Our research results provide a rapid, efficient and economic technical solution for the quality evaluation of ground improvement in soft soil subgrade reinforcement engineering.


Assuntos
Radar , Solo , Engenharia , Tecnologia
6.
Dalton Trans ; 52(13): 4058-4062, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36880436

RESUMO

A 2D Dy(III) metal-organic layer (MOL 1) was synthesized under solvothermal conditions. Structural analysis suggests that the Dy(III) ions in each one-dimensional (1D) arrangement are evenly arranged in the form of broken lines. The 1D chains are linked to one another via ligands to form a 2D layer that generates a 2D surface with elongated apertures. The photocatalytic activity study suggests that MOL 1 exhibits good catalytic activity in flavonoids by the formation of an O2˙- radical as an intermediate. This is the first reported method of synthesizing flavonoids using chalcones.

7.
Org Lett ; 25(12): 2078-2083, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-36946503

RESUMO

Despite the large number of synthetic macrocycles, the cubarenes, the quadrangular-shaped macrocyclic arenes, remain less investigated, possibly due either to synthetic challenges or to the lack of suitable building blocks. In this paper, a N-embedded cubarene (cub[4]indolocarbazole) is facilely synthesized by FeCl3·6H2O-catalyzed cyclization in dichloromethane. The endo cavity of cub[4]indolocarbazole can bury quaternary ammonium salts in an intramolecular manner, whereas the intermolecular interaction between its exo walls with Cu2+ generates two-dimensional supramolecular tessellation.

8.
Sci Total Environ ; 861: 160574, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36455746

RESUMO

The judgment of joint resistance action is significant for evaluating the resistance risk of antibacterial mixture. Using bacterial mutation frequency (MF) and conjugative transfer frequency (CTF) to respectively characterize the bacterial endogenous and exogenous resistance, mutation unit and conjugative transfer unit have been proposed to judge the joint resistance action of antibacterial mixture at a certain dose. However, these methods could not evaluate the antibacterial mixture's joint resistance action at a larger concentration-range. In this study, the concentration addition for bacterial resistance (CA-BR) approach was used to judge the joint resistance actions between kanamycin sulfate (KAN) and some other typical antibacterial agents, including sulfonamides (SAs), sulfonamide potentiators (SAPs), and silver antibacterial compounds (SACs). Through comparing the hormetic dose-response curves of the binary mixtures on the MF (or CTF) in Escherichia coli (E. coli) and the corresponding CA-BR curves calculated from the hormetic dose-responses of the single agents, the joint resistance actions between KAN and other agents were judged to exhibit dose-dependent feature: with the increase of mixture concentration, the joint mutation actions between KAN and SAs (or SAPs) were fixed at synergism, and the joint mutation actions between KAN and SACs varied from antagonism to synergism; the joint conjugative transfer actions between KAN and other agents changed from antagonism to synergism. Mechanistic explanation suggested that the heterogeneous pattern of joint resistance action had a close relationship with the interplays among the agents' modes of action, and meanwhile was significantly influenced by their joint survival pressure on E. coli. This study reveals the dose-dependent feature for the joint resistance action of antibacterial mixture and highlights the importance of exposure concentration, which will benefit clarifying the resistance risk of antibacterial mixture in the environment.


Assuntos
Escherichia coli , Hormese , Antibacterianos/toxicidade , Interações Medicamentosas , Sulfanilamida/farmacologia
10.
Ann Palliat Med ; 11(3): 1068-1076, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35365036

RESUMO

BACKGROUND: Flap repair is often required when repairing soft tissue defects in the lower limbs. Although early postoperative pain management (EPPM) can improve postoperative comfort and rest efficiency, and reduce the probability of complications, it cannot detect tissue blood circulation disorders in time. The purpose of this study was to explore the application value of EPPM combined with skin temperature monitoring (STM) after flap repair of soft tissue defects in the lower limbs. METHODS: We retrospectively collected the data of 101 patients who underwent lower limb soft tissue defect flap repair, which were divided into the EPPM group (n=50 cases) and the EPPM-STM group (n=51 cases). The EPPM group was given early postoperative pain management, and the EPPM-STM group was given additional skin temperature monitoring on the basis of the EPPM group. The clinical effect, reoperation rate, flap survival rate, pain score, postoperative quality of life and mental resilience, and complications were analyzed and compared. RESULTS: The average healing time of the EPPM-STM group was significantly lower compared with the EPPM group, and the serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) levels were significantly lower after the intervention (t=7.418, 3.447, 7.472; P<0.001, =0.001, <0.001). Compared with the EPPM group, the reoperation rate and complication rate in the EPPM-STM group were significantly lower, and the flap survival rate was significantly higher (χ2=6.966, 7.358; P=0.008, 0.007). The pain scores of the EPPM-STM group were significantly lower than those of the EPPM group after intervention (At 3 days: t=4.723; P<0.001. At 5 days: t=5.261; P<0.001), while the mental resilience and quality of life scores were significantly higher (t=-12.942, -9.975; P<0.001, <0.001). Logistic regression analysis showed that the postoperative management methods and the area of the flap defect were independent risk factors that affected the survival of the flap (t=7.358, 4.819; P=0.007, 0.028). CONCLUSIONS: EPPM combined with STM can increase the speed of postoperative healing, increase the survival rate of skin flaps, reduce the rate of reoperation and complications, and improve the quality of life and mental resilience of patients who undergo flap repair.


Assuntos
Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles , Humanos , Extremidade Inferior/lesões , Extremidade Inferior/cirurgia , Dor Pós-Operatória/prevenção & controle , Qualidade de Vida , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Temperatura Cutânea , Lesões dos Tecidos Moles/cirurgia
12.
J Cell Mol Med ; 25(16): 7608-7620, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34232553

RESUMO

Thyroid cancer (TC) was the most frequent thyroid malignant tumour, accounting for about 1% of all malignant tumours. Some long non-coding RNAs (lncRNAs) have been reported to exert essential tumour promotion effects, while caspase-9 (CASP9) gene could play a promotive role in the cell apoptosis in TC. However, whether they have a specific effect on TC remains unclear. Hence, this study aims to explore the relationship between LINC00607 and CASP9, and its effect in TC. LINC00607 expression in the TC tissues and cell lines was determined. Then, we explored the combination effect between a LINC00607 and a methylation inhibitor 5-Aza-dc in doxorubicin-resistant ARO cells using colony formation assay, flow cytometry, WST-1 and EdU assay, as well as in vivo tumour growth assay. Besides, the dual-luciferase reporter gene assay, RIP, ChIP, methylation-specific PCR and BSP method were employed to detect the relationship between LINC00607 and CASP9 and its methylation. LINC00607 expression was up-regulated in the doxorubicin-resistant TC cell lines and tissues and negatively correlated to the poor prognosis of TC patients. Knockdown of LINC00607 suppressed doxorubicin resistance, proliferation and colony formation, and promoted cell apoptosis of TC cells in vitro, as well as suppressed tumour growth in vivo, whereas LINC00607 overexpression was observed to exercise the opposite effects. Notably, it was also revealed that LINC00607 down-regulated the CASP9 expression by promoting CASP9 promoter methylation. In conclusion, LINC00607 could inhibit the apoptosis and augment the doxorubicin resistance of TC cells by decreasing CASP9 expression, which might provide a novel therapeutic target for TC treatment.


Assuntos
Caspase 9/genética , Metilação de DNA , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide/patologia , Animais , Apoptose , Caspase 9/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Inibidores da Topoisomerase II/farmacologia , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Plant Sci ; 310: 110956, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34315582

RESUMO

The dormancy-associated MADS-box (DAM) gene DAM5 has crucial roles in bud endodormancy; however, the molecular regulatory mechanism of PpDAM5 in peach (Prunus persica) has not been elucidated. In this study, using yeast two-hybrid screening, we isolated a BTB-TAZ Domain Protein PpBT3, which interacts with PpDAM5 protein, in the peach cultivar 'Chun xue'. As expected, we found that abscisic acid (ABA) maintained bud endodormancy and induced expression of the PpDAM5 gene, and that over-expressing PpDAM5 in Arabidopsis thaliana repressed seed germination. In contrast, over-expressing PpBT3 in A. thaliana promoted seed germination, and conferred resistance to ABA-mediated germination inhibition. Additionally, a qRT-PCR (quantitative real-time polymerase chain reaction) experiment suggested that the transcript level of PpBT3 gradually increased towards the endodormancy release period, which is the opposite trend of the expression pattern of PpDAM5. Our results suggest that PpBT3 modulates peach bud endodormancy by interacting with PpDAM5, thus revealing a new mechanism for regulating bud dormancy of perennial deciduous trees.


Assuntos
Flores/efeitos dos fármacos , Flores/metabolismo , Proteínas de Plantas/metabolismo , Prunus persica/efeitos dos fármacos , Prunus persica/metabolismo , Ácido Abscísico/farmacologia , Flores/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/genética , Prunus persica/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Sci Total Environ ; 786: 147464, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-33965827

RESUMO

Silver antibacterial compounds (SACs) and quorum sensing inhibitors (QSIs), as the potential antibiotic substitutes, have been recommended to prevent and treat microbial infections for the purpose of controlling the increasingly serious bacterial resistance induced by the abuse of antibiotics. However, there is little information regarding the resistance risk of these compounds, especially their mixtures. In this study, bacterial mutation and RP4 plasmid conjugative transfer among bacteria were used to characterize the bacterial endogenous and exogenous resistance, respectively. The effects of SACs (including silver nitrate (AgNO3) and silver nanoparticle (AgNP)), QSIs, and their binary mixtures on the bacterial resistance were investigated via setting the frequency of mutation and conjugative transfer in Escherichia coli (E. coli) as the test endpoints. The results indicated that these two endpoints exhibited hormetic dose-responses to each treatment. Furthermore, the joint resistance actions between SACs and QSIs were all judged to be antagonism. Correlation analysis suggested that the promotion of the bacterial resistance in each treatment was closely related to its toxicity. It was speculated that AgNO3 and AgNP might both release Ag+ ions to facilitate the E. coli resistance, while QSIs probably acted on LsrR and SdiA proteins to stimulate the bacterial mutation and accelerate the RP4 plasmid conjugative transfer, respectively. These findings imply that the bacteria may generate targeted stress response to the survival pressure from environmental compounds, displaying hormetic phenomenon in resistance-related test endpoints. This study provides a new insight into the resistance risk induced by SACs and QSIs, benefiting the environmental risk assessment of these compounds from the perspective of bacterial resistance.


Assuntos
Nanopartículas Metálicas , Percepção de Quorum , Antibacterianos/toxicidade , Escherichia coli , Hormese , Prata/toxicidade , Sulfonamidas/farmacologia
15.
Plant Physiol Biochem ; 142: 363-371, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398585

RESUMO

Nitrogen is one of the most important nutrients for plant growth and development. Nitrate nitrogen (NO3--N) is the main form of nitrogen taken up by plants. Understanding the effects of exogenous NO3--N on nitrogen metabolism at the gene expression and enzyme activity levels during nitrogen assimilation and chlorophyll synthesis is important for increasing nitrogen utilization efficiency. In this study, cell morphology, NO3--N uptake rates, the expression of key genes related to nitrogen assimilation and chlorophyll synthesis and enzyme activity in apple leaves under NO3--N deficiency were investigated. The results showed that the cell morphology of apple leaves was irreversibly deformed due to NO3--N deficiency. NO3--N was absorbed slightly one day after NO3--N deficiency treatment and effluxed after 3 days. The relative expression of genes encoding nitrogen assimilation enzymes and the activity of such enzymes decreased significantly after 1 day of NO3--N deficiency treatment. After treatment for 14 days, gene expression was upregulated, enzyme activity was increased, and NO3--N content was increased. NO3--N deficiency hindered the transformation of 5-aminobilinic acid (ALA) to porphobilinogen (PBG), suggesting a possible route by which NO3--N levels affect chlorophyll synthesis. Collectively, the results indicate that NO3--N deficiency affects enzyme activity by altering the expression of key genes in the nitrogen assimilation pathway, thereby suppressing NO3--N absorption and assimilation. NO3--N deficiency inhibits the synthesis of the chlorophyll precursor PBG, thereby hindering chlorophyll synthesis.


Assuntos
Clorofila/biossíntese , Malus/metabolismo , Nitratos/metabolismo , Folhas de Planta/metabolismo , Regulação da Expressão Gênica de Plantas , Malus/anatomia & histologia , Nitratos/análise , Nitrogênio/deficiência , Folhas de Planta/anatomia & histologia , Folhas de Planta/química , Reação em Cadeia da Polimerase em Tempo Real
16.
Nucleic Acids Res ; 46(9): 4560-4574, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29590477

RESUMO

Translesion DNA synthesis (TLS) is one mode of DNA damage tolerance that uses specialized DNA polymerases to replicate damaged DNA. DNA polymerase η (Polη) is well known to facilitate TLS across ultraviolet (UV) irradiation and mutations in POLH are implicated in skin carcinogenesis. However, the basis for recruitment of Polη to stalled replication forks is not completely understood. In this study, we used an affinity purification approach to isolate a Polη-containing complex and have identified SART3, a pre-mRNA splicing factor, as a critical regulator to modulate the recruitment of Polη and its partner RAD18 after UV exposure. We show that SART3 interacts with Polη and RAD18 via its C-terminus. Moreover, SART3 can form homodimers to promote the Polη/RAD18 interaction and PCNA monoubiquitination, a key event in TLS. Depletion of SART3 also impairs UV-induced single-stranded DNA (ssDNA) generation and RPA focus formation, resulting in an impaired Polη recruitment and a higher mutation frequency and hypersensitivity after UV treatment. Notably, we found that several SART3 missense mutations in cancer samples lessen its stimulatory effect on PCNA monoubiquitination. Collectively, our findings establish SART3 as a novel Polη/RAD18 association regulator that protects cells from UV-induced DNA damage, which functions in a RNA binding-independent fashion.


Assuntos
Antígenos de Neoplasias/metabolismo , Dano ao DNA , DNA/biossíntese , Proteínas de Ligação a RNA/metabolismo , Motivos de Aminoácidos , Antígenos de Neoplasias/química , Antígenos de Neoplasias/genética , Linhagem Celular , DNA de Cadeia Simples/biossíntese , Proteínas de Ligação a DNA/metabolismo , DNA Polimerase Dirigida por DNA/metabolismo , Humanos , Mutação de Sentido Incorreto , Neoplasias/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Multimerização Proteica , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/genética , Proteína de Replicação A/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Raios Ultravioleta
17.
Biochim Biophys Acta Proteins Proteom ; 1866(3): 464-472, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29196234

RESUMO

Environmental stresses are important factors causing male infertility which attracts broad attention. Protein acetylation is a pivotal post-translational modification and modulates diverse physiological processes including spermatogenesis. In this study, we employed quantitative proteomic techniques and bioinformatics tools to analyze the alterations of acetylome profile of mouse testis after heat shock and X-irradiation. Overall, we identified 1139 lysine acetylation sites in 587 proteins in which 1020 lysine acetylation sites were quantified. The Gene Ontology analysis showed that the major acetylated protein groups were involved in generation of precursor metabolites and metabolic processes, and were localized predominantly in cytosolic and mitochondrial. Compared to the control group, 36 sites of 28 acetylated proteins have changed after heat shock, and 49 sites of 43 acetylated proteins for X-ray exposure. Some of the differentially acetylated proteins have been reported to be associated with the progression of spermatogenesis and male fertility. We observed the up-regulated acetylation level change on testis specific histone 2B and heat shock protein upon heat treatment and a sharp decline of acetylation level on histone H2AX under X-ray treatment, suggesting their roles in male germ cells. Notably, the acetylation level on K279 of histone acetyltransferase (Kat7) was down-regulated in both heat and X-ray treatments, indicating that K279 may be a key acetylated site and affect its functions in spermatogenesis. Our results reveal that protein acetylation might add another layer of complexity to the regulation for spermatogenesis, and further functional studies of these proteins will help us elucidate the mechanisms of abnormal spermatogenesis.


Assuntos
Temperatura Alta , Lisina/metabolismo , Proteômica/métodos , Testículo/metabolismo , Testículo/efeitos da radiação , Acetilação/efeitos da radiação , Sequência de Aminoácidos , Animais , Sítios de Ligação , Biologia Computacional , Resposta ao Choque Térmico/efeitos da radiação , Lisina/química , Masculino , Camundongos Endogâmicos C57BL , Modelos Moleculares , Domínios Proteicos , Proteoma/química , Proteoma/metabolismo , Espectrometria de Massas em Tandem
18.
Nat Commun ; 8(1): 1941, 2017 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-29208956

RESUMO

DNA polymerase η (Polη) facilitates translesion DNA synthesis (TLS) across ultraviolet (UV) irradiation- and cisplatin-induced DNA lesions implicated in skin carcinogenesis and chemoresistant phenotype formation, respectively. However, whether post-translational modifications of Polη are involved in these processes remains largely unknown. Here, we reported that human Polη undergoes O-GlcNAcylation at threonine 457 by O-GlcNAc transferase upon DNA damage. Abrogation of this modification results in a reduced level of CRL4CDT2-dependent Polη polyubiquitination at lysine 462, a delayed p97-dependent removal of Polη from replication forks, and significantly enhanced UV-induced mutagenesis even though Polη focus formation and its efficacy to bypass across cyclobutane pyrimidine dimers after UV irradiation are not affected. Furthermore, the O-GlcNAc-deficient T457A mutation impairs TLS to bypass across cisplatin-induced lesions, causing increased cellular sensitivity to cisplatin. Our findings demonstrate a novel role of Polη O-GlcNAcylation in TLS regulation and genome stability maintenance and establish a new rationale to improve chemotherapeutic treatment.


Assuntos
Dano ao DNA , Reparo do DNA , DNA Polimerase Dirigida por DNA/metabolismo , DNA/biossíntese , N-Acetilglucosaminiltransferases/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Replicação do DNA , Células HEK293 , Humanos , Mutagênese , Poliubiquitina , Processamento de Proteína Pós-Traducional , Dímeros de Pirimidina , Ubiquitinação , Raios Ultravioleta
19.
Oncotarget ; 8(22): 36423-36437, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28430587

RESUMO

Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD). Notably, PD patients also exhibit a significantly higher risk in melanoma and other skin tumors, while the mechanism remains largely unknown. In this study, we show that depletion of Parkin causes compromised cell viability and genome stability after ultraviolet (UV) radiation. We demonstrate that Parkin promotes efficient Rad18-dependent proliferating cell nuclear antigen (PCNA) monoubiquitination by facilitating the formation of Replication protein A (RPA)-coated ssDNA upon UV radiation. Furthermore, Parkin is found to physically interact with NBS1 (Nijmegen breakage syndrome 1), and to be required for optimal recruitment of NBS1 and DNA polymerase eta (Polη) to UV-induced damage sites. Consequently, depletion of Parkin leads to increased UV-induced mutagenesis. These findings unveil an important role of Parkin in protecting genome stability through positively regulating translesion DNA synthesis (TLS) upon UV damage, providing a novel mechanistic link between Parkin deficiency and predisposition to skin cancers in PD patients.


Assuntos
Reparo do DNA , Replicação do DNA/efeitos da radiação , Ubiquitina-Proteína Ligases/metabolismo , Raios Ultravioleta , Animais , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Proteínas de Ligação a DNA/metabolismo , Técnicas de Inativação de Genes , Instabilidade Genômica , Humanos , Camundongos , Mutagênese/efeitos da radiação , Mutação , Proteínas Nucleares/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ligação Proteica , Tolerância a Radiação/genética , Proteína de Replicação A/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação/efeitos da radiação
20.
Mol Med Rep ; 15(5): 2620-2624, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28447753

RESUMO

The present study demonstrated the effect of fucoidan, isolated from Fucus vesiculosus, on cell growth and apoptosis in anaplastic thyroid cancer cells. The cell viability was analyzed using a Cell Counting Kit­8 cell proliferation kit. Diamidino-2-phenylindole and terminal deoxynucleotidyl transferase-mediated dUTP nick­end labeling assays were used to examine the apoptotic effect of fucoidan, which revealed the presence of apoptotic bodies and DNA fragmentation. Fucoidan inhibited the growth of FTC133 and TPC1 ATC cells in a dose­dependent manner. It also induced the apoptosis of FTC133 cells by promoting the expression levels of cleaved poly ADP­ribose polymerase and caspase­3. Significant decreases in the levels expression of hypoxia-inducible factor 1α and vascular endothelial growth factor were observed in the FTC133 cells following treatment of the cells with fucoidan. In addition, inhibition in tube formation and the migration of FTC133 cells were observed in the cells treated with fucoidan, compared with the cells in the control group. Therefore, fucoidan inhibited cell growth, induced apoptosis and suppressed angiogenesis in the thyroid cancer cells.


Assuntos
Inibidores da Angiogênese/farmacologia , Apoptose/efeitos dos fármacos , Neovascularização Patológica , Polissacarídeos/farmacologia , Neoplasias da Glândula Tireoide , Linhagem Celular Tumoral , Células Endoteliais da Veia Umbilical Humana , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neoplasias da Glândula Tireoide/irrigação sanguínea , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia
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