RESUMO
Homologous recombination (HR) is a key process for repairing DNA double strand breaks and for promoting genetic diversity. However, HR occurs unevenly across the genome, and certain genomic features can influence its activity. One such feature is the presence of guanine quadruplexes (G4s), stable secondary structures widely distributed throughout the genome. These G4s play essential roles in gene transcription and genome stability regulation. Especially, elevated G4 levels in cells deficient in the Bloom syndrome helicase (BLM) significantly enhance HR at G4 sites, potentially threatening genome stability. Here, we investigated the role of G4-binding protein Yin Yang-1 (YY1) in modulating HR at G4 sites in human cells. Our results show that YY1's binding to G4 structures suppresses sister chromatid exchange after BLM knockdown, and YY1's chromatin occupancy negatively correlates with the overall HR rate observed across the genome. By limiting RAD51 homolog 1 (RAD51) access, YY1 preferentially binds to essential genomic regions, shielding them from excessive HR. Our findings unveil a novel role of YY1-G4 interaction, revealing novel insights into cellular mechanisms involved in HR regulation.
Assuntos
Quadruplex G , Recombinação Homóloga , Rad51 Recombinase , Troca de Cromátide Irmã , Fator de Transcrição YY1 , Humanos , Fator de Transcrição YY1/metabolismo , Fator de Transcrição YY1/genética , Recombinação Homóloga/genética , Rad51 Recombinase/metabolismo , Rad51 Recombinase/genética , Troca de Cromátide Irmã/genética , RecQ Helicases/metabolismo , RecQ Helicases/genética , Cromatina/metabolismo , Cromatina/genética , Quebras de DNA de Cadeia Dupla , Instabilidade Genômica/genéticaRESUMO
Chronic arsenic exposure is considered to increase the risk of breast cancer. p62 is a multifunctional adaptor protein that controls myriad cellular processes and is overexpressed in breast cancer tissues. Although previous studies have indicated the involvement of p62 accumulation in arsenic tumorigenesis, the underlying mechanism remains obscure. Here, we found that 0.1 µM or 0.5 µM arsenite exposure for 24 weeks induced oncogenic phenotypes in human mammary epithelial cells. Elevated aerobic glycolysis, cell proliferation capacity, and activation of p62-mTOR pathway, as indicated by increased protein levels of p62, phosphorylated-mTOR (p-mTOR) and hypoxia-inducible factor 1α (HIF1α), were observed in chronically arsenite-exposed cells, and of note in advance of the onset of oncogenic phenotypes. Moreover, p62 silencing inhibited acquisition of oncogenic phenotypes in arsenite-exposed cells. The protein levels of p-mTOR and HIF1α, as well as aerobic glycolysis and cell proliferation, were suppressed by p62 knockdown. In addition, re-activation of pmTOR reversed the inhibitory effects of p62 knockdown. Collectively, our data suggest that p62 exerts an oncogenic role via mTORC1 activation and acts as a key player in glucose metabolism during arsenite-induced malignant transformation, which provides a new mechanistic clue for the arsenite carcinogenesis.
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Arsênio , Arsenitos , Neoplasias da Mama , Humanos , Feminino , Arsênio/toxicidade , Arsenitos/toxicidade , Glicólise , Serina-Treonina Quinases TOR/metabolismo , Carcinogênese , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/metabolismo , Células Epiteliais/metabolismo , Linhagem Celular TumoralRESUMO
Chlorophenols are widespread environmental organic pollutants with harmful effects on human beings. Although relationships between chlorophenols and various dysfunctions/diseases have been reported, the contribution of chlorophenols exposure to mortalities is underdetermined. In this cohort study, we included 4 types of urinary chlorophenols, aiming to estimate associations of chlorophenols exposure with all-cause and cause-specific mortalities. Urinary chlorophenols were examined at baseline of National Health and Nutrition Examination Survey (NHANES) 2003-2010, and adjusted for the urinary creatinine level. Associations between chlorophenols and mortalities were estimated using COX regression analyses, results were shown as hazard ratio (HR) and 95% confidence interval (95% CI). By dividing participants into four subgroups based on quartiles of urinary levels of chlorophenols, associations between mortalities and categorical variables of chlorophenols were estimated. Furthermore, the quantile g-computation analysis was used to estimate the joint effects of 4 chlorophenols on mortalities. Among 5817 adults (2863 men), 1034 were deceased during the follow-up. After adjusted for confounders, 2,4,5-trichlorophenol (2,4,5-TCP) was found to be positively associated with both all-cause (HR = 1.46; 95% CI: 1.16, 1.84) and cardiovascular disease (CVD) mortalities (HR = 1.60; 95% CI: 1.00, 2.55). Compared to the subgroup of the lowest level of chlorophenols, participants in subgroups of higher 2,4,5-TCP levels showed higher risk of all-cause mortality (P-value for trend = 0.003). For CVD mortality, HRs in subgroups of higher levels of 2,4-dichlorophenol (2,4-DCP) and 2,4,6-trichlorophenol (2,4,6-TCP) were statistically significant (P-values for trend were 0.017 for 2,4-DCP and 0.049 for 2,4,6-TCP). The HRs (95% CI) of joint effects of 4 chlorophenols were 1.11 (1.01, 1.21) and 1.32 (1.10, 1.57) for all-cause and CVD-specific mortalities, and 2,4,5-TCP showed the highest weight in joint effects. All of these findings implied that among 4 urinary chlorophenols we included, 2,4,5-TCP might be a sensitive one in associations with mortalities among general populations.
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Doenças Cardiovasculares , Clorofenóis , Poluentes Ambientais , Adulto , Masculino , Humanos , Estados Unidos , Inquéritos Nutricionais , Estudos de Coortes , Doenças Cardiovasculares/urinaRESUMO
BACKGROUND: Published studies have shown positive associations of branched chain and aromatic amino acids with type 2 diabetes mellitus (T2DM), and the findings remain consistent. However, the associations of other essential and semi-essential amino acids, i.e., methionine (Met), threonine (Thr), lysine (Lys), arginine (Arg) and histidine (His), with T2DM remain unknown. Obesity is an important independent risk factor for T2DM, and excessive amino acids can convert into glucose and lipids, which might underlie the associations of amino acids with obesity. Therefore, we aimed to estimate the associations between dietary intakes of these 5 amino acids and T2DM risk, as well as the mediation effects of obesity on these associations, in a Chinese population. METHODS: A total of 10,920 participants (57,293 person-years) were included, and dietary intakes of 5 amino acids were investigated using 24-h dietary recalls. Anthropometric obesity indices were measured at both baseline and the follow-up endpoints. Associations of amino acids with T2DM were estimated using COX regression models, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were shown. The mediation effects of obesity indices were analyzed, and the proportion of the mediation effect was estimated. RESULTS: Higher intakes of the 5 amino acids were associated with increasing T2DM risk, while significant HRs were only shown in men after adjustments. No interaction by gender was found. Regression analyses using quintiles of amino acids intakes showed that T2DM risk was positively associated with amino acids intakes only when comparing participants with the highest intake levels of amino acids to those with the lowest intake levels. Adjusted correlation coefficients between amino acid intakes and obesity indices measured at follow-up endpoints were significantly positive. Mediation analyses showed that mediation effects of obesity indices existed on associations between amino acids intakes and T2DM risk, and the mediation effect of waist circumference remained strongest for each amino acid. CONCLUSIONS: We found positive associations of dietary intakes of Met, Thr, Lys, Arg and His with increasing T2DM risk in general Chinese residents, on which the mediation effect of obesity existed. These findings could be helpful for developing more constructive guidance in the primary prevention of T2DM based on dietary interventions.
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Diabetes Mellitus Tipo 2 , Dieta , Obesidade , Humanos , Masculino , Aminoácidos/efeitos adversos , Aminoácidos/metabolismo , Arginina , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , População do Leste Asiático , Histidina , Lisina , Metionina , Obesidade/epidemiologia , Obesidade/complicações , Racemetionina , Fatores de Risco , TreoninaRESUMO
Real-time imaging of multiple low-abundance microRNAs (miRNAs) simultaneously in living cells with high sensitivity is of vital importance for accurate cancer clinical diagnosis and prognosis studies. Maintaining stability of nanoprobes resistant to enzyme degradation and enabling effective signal amplification is highly needed for in vivo imaging studies. Herein, a rationally designed one-pot assembled multicolor tetrahedral DNA frameworks (TDFs) by encoding multicomponent nucleic acid enzymes (MNAzymes) was developed for signal-amplified multiple miRNAs imaging in living cells with high sensitivity and selectivity. TDFs could enter cells via self-delivery with good biocompatibility and stability. Two kinds of MNAzymes specific for miRNA-21 and miRNA-155 with fluorescein labeling were encoded in the structure of TDFs respectively through one-step thermal annealing. In the intracellular environment, the TDFs could be specifically bound with its specific miRNA target and form an active DNAzyme structure. The cleavage of the active site would trigger the release of target miRNA and circular fluorescence signal amplification, which enabled accurate diagnosis on miRNA identifications of different cell lines with high sensitivity. Meanwhile, with the specific AS1411 aptamer targeting for nucleolin overexpressed on the surface of the carcinoma cells, this well-designed TDFs nanoprobe exhibited good discrimination between cancer cells and normal cells. The strategy provides an efficient tool for understanding the biological function of miRNAs in cancer pathogenesis and therapeutic applications.
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DNA/química , MicroRNAs/química , Imagem Molecular/métodos , Linhagem Celular Tumoral , Sobrevivência Celular , Humanos , Espaço Intracelular/metabolismo , Microscopia de Força Atômica , Sondas Moleculares/química , Nanotecnologia/métodos , Conformação de Ácido NucleicoRESUMO
The storage of charges in organic light-emitting diodes (OLEDs) has drawn much attention for its damage to device performance as well as the loss to carriers. Thus, it is essential to address the issue and do further investigation. The traditional approach to storage analysis is mainly based on transient measurement since it is sensitive to transient instead of steady signal. In this paper, we proposed a new benchmark to investigate the single-layer OLEDs capable of stored charges with poly (methyl methacrylate) (PMMA), which is just based on electrical and optical characteristics. Since the stored charges contribute both to luminance and current of the devices with PMMA, the area between them can be taken as a benchmark and evaluated the storage of charges. In our experiment, the areas of 4 nm, 6 nm, 8 nm, and 10 nm PMMA devices are 0.348, 0.554, 0.808, and 0.894, respectively, indicating a higher capability of storage in thicker PMMA. It is exactly in line with the results taken from transient electroluminescence (EL) measurement. Thus, this new benchmark is practical and provides a more accessible approach to investigate the storage of charges in OLEDs.
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Eletricidade , Luz , Fenômenos Ópticos , Polimetil Metacrilato/química , Semicondutores , Benchmarking , Desenho de EquipamentoRESUMO
BACKGROUND: Colonic polyps are more likely to be cancerous, especially those with large diameter, large number and atypical hyperplasia. If colonic polyps cannot be treated in early stage, they are likely to develop into colon cancer. Colonoscopy is easily limited by the operator's experience, and factors such as inexperience and visual fatigue will directly affect the accuracy of diagnosis. Cooperating with Hunan children's hospital, we proposed and improved a deep learning approach with global average pooling (GAP) in colonoscopy for assisted diagnosis. Our approach for assisted diagnosis in colonoscopy can prompt endoscopists to pay attention to polyps that may be ignored in real time, improve the detection rate, reduce missed diagnosis, and improve the efficiency of medical diagnosis. METHODS: We selected colonoscopy images from the gastrointestinal endoscopy room of Hunan children's hospital to form the colonic polyp datasets. And we applied the image classification method based on Deep Learning to the classification of Colonic Polyps. The classic networks we used are VGGNets and ResNets. By using global average pooling, we proposed the improved approaches: VGGNets-GAP and ResNets-GAP. RESULTS: The accuracies of all models in datasets exceed 98%. The TPR and TNR are above 96 and 98% respectively. In addition, VGGNets-GAP networks not only have high classification accuracies, but also have much fewer parameters than those of VGGNets. CONCLUSIONS: The experimental results show that the proposed approach has good effect on the automatic detection of colonic polyps. The innovations of our method are in two aspects: (1) the detection accuracy of colonic polyps has been improved. (2) our approach reduces the memory consumption and makes the model lightweight. Compared with the original VGG networks, the parameters of our VGG19-GAP networks are greatly reduced.
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Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Diagnóstico por Computador/métodos , Adolescente , Criança , Pré-Escolar , China , Bases de Dados Factuais , Aprendizado Profundo , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Sensibilidade e EspecificidadeRESUMO
In this paper, capacitance/conductance-voltage characteristics (C/G-V) under illumination was achieved to investigate the dynamic mechanism of stored charges in OLEDs with a structure of ITO/ PEDOT:PSS/PMMA/Alq3/Al. For all devices, at least two peaks presented in the optical capacitance-voltage curve. Compared to curves of devices under dark, the first peak increased remarkably with a deviation to Vbi, which can be explained in the form of stored charges combined with the optical conductance characteristics. It was also found that a great decrease in capacitance is followed by the collapse of the first peak with PMMA thickness increased. It can account for the presence of interfacial charges, which is proved further by the conductance curves. To the device with 10 nm PMMA, a third peak took place in optical capacitance and it was due to the storage of electrons by PMMA. Also, the first capacitance peak enhanced approximate linearly as the illumination power increased, which can verify the contribution of the stored charges. Additionally, it shows the potential for the stored charges in optical detections.
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Capacitância Elétrica , Luz , Iluminação , SemicondutoresRESUMO
The accumulation carriers and the trapped carriers are found in many organic light-emitting diodes (OLEDs) more or less, which can lead to a great loss of carriers and weaken the performance of devices. We have investigated a host-guest-system containing the green phosphorescent emitter tris[2-phenylpyridinato-C2,N]iridium(â ¢) [Ir(ppy)3] and one host material with transient electroluminescence (EL). The charge recombination, accumulation and light emission mechanisms of the phosphorescent organic light-emitting diodes (PhOLEDs) with different host materials were analyzed. The structure was fabricated as ITO/NPB(30 nm)/host: Ir(ppy)3/BCP(10 nm)/Alq3(20 nm)/LiF(0.7 nm)/Al(100 nm),the hosts were CBP, PVK and TAZ respectively. These results showed the transient EL was strongly dependent on host materials. Compared to devices of host material CBP and PVK, only those with the host material TAZ as the emitting layer exhibited strong electroluminescence overshoots between 1 and 3 µs after turning off the voltage pulse at room temperatures. To further elucidate the generality of the overshoots, we monitored their dependence on the dopant concentration. The transient EL results in host-guest-system devices demonstrated a direct link between the strong overshoot effect and charge trapping in the emitting guest molecules. The excessive electrons in the guest sites could be a major factor inducing significant strong overshoot phenomenon in the TAZ: Ir(ppy)3 layer. We attributed these overshoot effect to the electrons accumulated on Ir(ppy)3 sites and accumulated holes in the vicinity of the HBL/EML interface. As a result, we obtained a better understanding of carriers' dynamics and recombination process of PhOLEDs after turning off the voltage pules. The new understanding of the charge carriers and exciton dynamics of PhOLEDs is instrumental in directing the efforts of developing stable and high-efficiency PhOLEDs.
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Cor , Temperatura , IluminaçãoRESUMO
Raltitrexed has shown efficacy and safety in many tumor types; however, the clinical data on the treatment of hepatocellular carcinoma is rare. In this report, we aim to assess the efficacy and safety of raltitrexed plus oxaliplatin (OXA)-based transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (uHCC). Patients with uHCC were recruited from multi-centers in China and assigned randomly to raltitrexed+OXA-based (n=76), fluorouracil+OXA-based (n=76), and doxorubicin+OXA-based (n=75) TACE treatment. The primary end point was overall survival (OS). Tumor response was assessed using response evaluation criteria in solid tumors (RECIST), modified response evaluation criteria in solid tumors (mRECIST), and European Association for the Study of the Liver criteria (EASL). Safety and toxicity were evaluated using the National Cancer Institute Common Toxicity Criteria. The raltitrexed group showed a better disease control rate evaluated using RECIST (raltitrexed vs. fluorouracil vs. doxorubicin: 96.1 vs. 84.2 vs. 86.7%, P=0.05) and a better overall response rate on the basis of mRECIST (67.1 vs. 47.4 vs. 50.7%, P=0.03) and EASL (67.1 vs. 47.4 vs. 49.3%, P=0.02). The median OS and median progression-free survival (PFS) were higher in the raltitrexed group (median OS: 13.4 vs. 9.6 vs. 8.5 months; median PFS: 6.7 vs 4.9 vs 4.6 months). The most common toxicities included elevated aspartate aminotransferase (78.9 vs. 86.8 vs. 81.3%) and abdominal nonspecific pain (68.4 vs. 81.6 vs. 78.7%). No significant differences were found in the overall number of patients who experienced any toxicity. Raltitrexed plus OXA-based TACE suggested a safe and efficacious regimen in uHCC patients. The results warrant further clinical investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Adulto , Idoso , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Quinazolinas/administração & dosagem , Tiofenos/administração & dosagem , Adulto JovemRESUMO
BACKGROUND/AIMS: Our previous study has demonstrated that down-regulation of miR-376a might contribute to the development of hepatocellular carcinoma (HCC), but the mechanism underlying this down-regulation remains obscure. METHODS/RESULTS: histone deacetylase (HDAC) inhibitor increased the level of miR-376a in L02 and Huh7 cells by up-regulating the acetylation level of histone 3 at the Maternally expressed 3 (Meg3) differentially methylated region (DMR). Interestingly, HDAC9, a histone deacetylase responsible for deacetylating lysine 18 of histone 3 (H3K18), was identified as the target of miR-376a. In addition, HDAC9 siRNA increased the expression of miR-376a by up-regulating the global histone H3K18 acetylation level, with Meg3 DMR included. Finally, miR-376a and HDAC9 were inversely correlated in HCC. CONCLUSION: HDAC9 plays an important role both as effects and targets of miR-376a.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Histona Desacetilases/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteínas Repressoras/genética , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Decitabina , Regulação para Baixo/efeitos dos fármacos , Epigênese Genética , Histona Desacetilases/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , Mutação , Proteínas Repressoras/metabolismoRESUMO
OBJECTIVE: To investigate the roles of phosphatidylinositol 3 kinase regulatory subunit alpha (PIK3R1ï¼gene in the development of hepatocellular carcinoma ï¼HCCï¼. METHODS: Surgical specimens of liver cancer and corresponding pericancerous liver tissue were collected from 20 patients with hepatocellular carcinoma. Expression of p85α, encoded by PIK3R1, in HCC tissue specimens was detected by Western blotting and immunohistochemistry. HCC HepG2 cells were transfected with PIK3R1 siRNA or PIK3R1-cDNA. The expression of PIK3R1 in transfected HepG2 cells or control cells were detected by real-time PCR. Cell proliferation was evaluated by MTT, colony formation assays and flow cytometry respectively. The expression of PI3K/AKT pathway-related proteins were detected by Western blotting. RESULTS: The expression of p85α in liver tissue was higher than that in pericancerous tissues (1.27±0.58 vs 0.99±0.47ï¼t=-3.25ï¼P<0.05ï¼. The expression of PIK3R1 was decreased by 0.19±0.03 fold in PIK3R1siRNA-transfected HepG2 cells(t=46.77ï¼P<0.05)ï¼and increased by 32.36±3.33 fold in PIK3R1 cDNA -transfected cellsï¼t=-16.31ï¼ P<0.05ï¼. MTT result showed that PIK3R1 siRNA inhibited growth of HepG2 cells ï¼0.611±0.072 vs 0.807±0.059ï¼t=3.65ï¼P<0.05ï¼ï¼while PIK3R1 cDNA increased the cell growthï¼0.937±0.060 vs 0.693±0.065ï¼t=-4.78ï¼P<0.05ï¼. PIK3R1 siRNA transfected cells presented lower colony-forming efficiency than control groupï¼3.8%±0.84% vs 15.0%±2.3%ï¼t=7.92ï¼P<0.05ï¼ï¼while PIK3R1 cDNA transfected cells had higher colony-forming efficiency than control group (23.6%±3.4% vs 12.0%±1.5%ï¼t=-5.40ï¼P<0.05ï¼. PIK3R1 siRNA reduced the ratio of S phase cellsï¼13.9%±0.015% vs 32.9%±0.07%ï¼t=45.97ï¼P<0.01, while PIK3R1 cDNA increased S phase cellsï¼56.33%±0.024% vs 31.94%±0.042%ï¼t=-8.73ï¼P<0.01ï¼. PIK3R1 increased the level of p-AKT and decreased p53 level. CONCLUSIONï¼p85α is highly expressed in HCCï¼and PIK3R1 gene may promote proliferation of HepG2 cells by activating PI3K/AKT pathway.
Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Fosfatidilinositol 3-Quinases/genética , Proliferação de Células , Classe Ia de Fosfatidilinositol 3-Quinase , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Proteínas , RNA Interferente Pequeno , TransfecçãoRESUMO
Porcine orthoreoviruses belong to the family Reoviridae and cause mainly mild enteritis in piglets. We present here the complete genome sequence of a novel porcine orthoreovirus strain (GD-1) isolated from a piglet in southern China. Our data will facilitate future investigations of the molecular characteristics and epidemiology of porcine orthoreoviruses.
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Genoma Viral , Orthoreovirus/genética , Animais , Chlorocebus aethiops , Bases de Dados Genéticas , Enterite/virologia , Genes Virais , Dados de Sequência Molecular , RNA Viral , Análise de Sequência de DNA , Suínos , Células VeroRESUMO
The COVID-19 pandemic has significantly impacted the healthcare industry, especially public health resources and resource allocation. With the change in people's lifestyles and increased demand for medical and health care in the post-pandemic era, the Internet and home healthcare have rapidly developed. As an essential part of Internet healthcare, mobile health (mHealth) applications help to fundamentally address the lack of medical resources and meet people's healthcare needs. In this mixed-method study, we conducted in-depth interviews with 20 users in China (mean age = 26.13, SD = 2.80, all born in China) during the pandemic, based on the unified theory of acceptance and use of technology 2 (UTAUT-2) mode, and identified four dimensions of user needs in mHealth scenarios: convenience, control, trust, and emotionality. Based on the interview results, we adjusted the independent variables, deleted the hedonic motivation and the habit, and added the perceived trust and perceived risk as the variables. Using a structural equation model (SEM), we designed the questionnaire according to the qualitative results and collected data from 371 participants (above 18 years old, 43.9% male) online to examine the interrelationships these variables. The results show that performance expectancy (ß = 0.40, p < 0.001), effort expectancy (ß = 0.40, p < 0.001), social influence (ß = 0.14, p < 0.05), facilitating condition (ß = 0.15, p < 0.001), and perceived trust (ß = 0.31, p < 0.001) had positive effects on use intention. Perceived risk (ß = -0.31, p < 0.001) harmed use intention, and price value (ß = 0.10, p > 0.5) had no significant effects on use intention. Finally, we discussed design and development guidelines that can enhance user experience of mHealth applications. This research combines the actual needs and the main factors affecting the use intention of users, solves the problems of low satisfaction of user experience, and provides better strategic suggestions for developing mHealth applications in the future.
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COVID-19 , Aplicativos Móveis , Telemedicina , Humanos , Masculino , Adulto , Adolescente , Feminino , Intenção , Pandemias , Aceitação pelo Paciente de Cuidados de Saúde , ChinaRESUMO
Herein, we present a poly-adenine (polyA)-mediated programmably engineered FRET-nanoflare for ratiometric intracellular ATP imaging with anti-interference capability. The programmable polyA attachment is advantageous in enhancing the signal response for ATP. Moreover, the FRET-based nanoflare is capable of avoiding false-positive signals due to probe degradation in a complex environment, which has great potential for clinical diagnosis.
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Diagnóstico por Imagem , Transferência Ressonante de Energia de Fluorescência , Transferência Ressonante de Energia de Fluorescência/métodos , Trifosfato de Adenosina , Corantes FluorescentesRESUMO
BACKGROUND: Newcastle disease virus (NDV) is an enveloped RNA virus, bearing severe economic losses to the poultry industry worldwide. Previous virion proteomic studies have shown that enveloped viruses carry multiple host cellular proteins both internally and externally during their life cycle. To address whether it also occurred during NDV infection, we performed a comprehensive proteomic analysis of highly purified NDV La Sota strain particles. RESULTS: In addition to five viral structural proteins, we detected thirty cellular proteins associated with purified NDV La Sota particles. The identified cellular proteins comprised several functional categories, including cytoskeleton proteins, annexins, molecular chaperones, chromatin modifying proteins, enzymes-binding proteins, calcium-binding proteins and signal transduction-associated proteins. Among these, three host proteins have not been previously reported in virions of other virus families, including two signal transduction-associated proteins (syntenin and Ras small GTPase) and one tumor-associated protein (tumor protein D52). The presence of five selected cellular proteins (i.e., ß-actin, tubulin, annexin A2, heat shock protein Hsp90 and ezrin) associated with the purified NDV particles was validated by Western blot or immunogold labeling assays. CONCLUSIONS: The current study presented the first standard proteomic profile of NDV. The results demonstrated the incorporation of cellular proteins in NDV particles, which provides valuable information for elucidating viral infection and pathogenesis.
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The dietary intake of branched-chain amino acids (BCAAs) has been reported to be associated with both elevated blood pressure (BP) and hypertension risk, while published findings were inconsistent, and the causality has never been well disclosed. We performed this prospective study aiming to find out the relationship between dietary BCAAs intake and hypertension risk in the Chinese population. A total of 8491 participants (40,285 person-years) were selected. The levels of dietary BCAAs intake were estimated using the 24-h Food Frequency Questionnaire. Associations of both BP values and hypertension risk with per standard deviation increase of BCAAs were estimated using linear and COX regression analysis, respectively. The hazard ratios and 95% confidence interval were given. Restricted cubic spline analysis (RCS) was used to estimate the nonlinearity. Both systolic and diastolic BP values at the end points of follow-up were positively associated with dietary BCAAs intake. Positive associations between BCAAs intake and hypertension risk were shown in both men and women. By performing a RCS analysis, the nonlinear relationship between BCAAs intake and hypertension was shown. As the intake levels of Ile, Leu, and Val, respectively, exceeded 2.49 g/day, 4.91 g/day, and 2.88 g/day in men (2.16 g/day, 3.84 g/day, and 2.56 g/day in women), the hypertension risk increased. Our findings could provide some concrete evidence in the primary prevention of hypertension based on dietary interventions.
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Aminoácidos de Cadeia Ramificada , Hipertensão , China/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
BACKGROUND: Infectious bronchitis virus (IBV) is the coronavirus of domestic chickens causing major economic losses to the poultry industry. Because of the complexity of the IBV life cycle and the small number of viral structural proteins, important virus-host relationships likely remain to be discovered. Toward this goal, we performed two-dimensional gel electrophoresis fractionation coupled to mass spectrometry identification approaches to perform a comprehensive proteomic analysis of purified IBV particles. RESULTS: Apart from the virus-encoded structural proteins, we detected 60 host proteins in the purified virions which can be grouped into several functional categories including intracellular trafficking proteins (20%), molecular chaperone (18%), macromolcular biosynthesis proteins (17%), cytoskeletal proteins (15%), signal transport proteins (15%), protein degradation (8%), chromosome associated proteins (2%), ribosomal proteins (2%), and other function proteins (3%). Interestingly, 21 of the total host proteins have not been reported to be present in virions of other virus families, such as major vault protein, TENP protein, ovalbumin, and scavenger receptor protein. Following identification of the host proteins by proteomic methods, the presence of 4 proteins in the purified IBV preparation was verified by western blotting and immunogold labeling detection. CONCLUSIONS: The results present the first standard proteomic profile of IBV and may facilitate the understanding of the pathogenic mechanisms.
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BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped virus, bearing severe economic consequences to the swine industry worldwide. Previous studies on enveloped viruses have shown that many incorporated cellular proteins associated with the virion's membranes that might play important roles in viral infectivity. In this study, we sought to proteomically profile the cellular proteins incorporated into or associated with the virions of a highly virulent PRRSV strain GDBY1, and to provide foundation for further investigations on the roles of incorporated/associated cellular proteins on PRRSV's infectivity. RESULTS: In our experiment, sixty one cellular proteins were identified in highly purified PRRSV virions by two-dimensional gel electrophoresis coupled with mass spectrometric approaches. The identified cellular proteins could be grouped into eight functional categories including cytoskeletal proteins, chaperones, macromolecular biosynthesis proteins, metabolism-associated proteins, calcium-dependent membrane-binding proteins and other functional proteins. Among the identified proteins, four have not yet been reported in other studied envelope viruses, namely, guanine nucleotide-binding proteins, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase, peroxiredoxin 1 and galectin-1 protein. The presence of five selected cellular proteins (i.e., ß-actin, Tubulin, Annexin A2, heat shock protein Hsp27, and calcium binding proteins S100) in the highly purified PRRSV virions was validated by Western blot and immunogold labeling assays. CONCLUSIONS: Taken together, the present study has demonstrated the incorporation of cellular proteins in PRRSV virions, which provides valuable information for the further investigations for the effects of individual cellular proteins on the viral replication, assembly, and pathogenesis.
Assuntos
Vírus da Síndrome Respiratória e Reprodutiva Suína/química , Vírus da Síndrome Respiratória e Reprodutiva Suína/isolamento & purificação , Proteínas/análise , Proteoma/análise , Vírion/química , Vírion/isolamento & purificação , Animais , Western Blotting , Linhagem Celular , Chlorocebus aethiops , Eletroforese em Gel Bidimensional , Microscopia Imunoeletrônica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
With the wide application of high-resolution radar, the application of Radar Automatic Target Recognition (RATR) is increasingly focused on how to quickly and accurately distinguish high-resolution radar targets. Therefore, Synthetic Aperture Radar (SAR) image recognition technology has become one of the research hotspots in this field. Based on the characteristics of SAR images, a Sparse Data Feature Extraction module (SDFE) has been designed, and a new convolutional neural network SSF-Net has been further proposed based on the SDFE module. Meanwhile, in order to improve processing efficiency, the network adopts three methods to classify targets: three Fully Connected (FC) layers, one Fully Connected (FC) layer, and Global Average Pooling (GAP). Among them, the latter two methods have less parameters and computational cost, and they have better real-time performance. The methods were tested on public datasets SAR-SOC and SAR-EOC-1. The experimental results show that the SSF-Net has relatively better robustness and achieves the highest recognition accuracy of 99.55% and 99.50% on SAR-SOC and SAR-EOC-1, respectively, which is 1% higher than the comparison methods on SAR-EOC-1.