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Objective: To clarify the mechanism of Fat1 on the proliferation of esophageal squamous cell carcinoma (ESCC). Methods: KYSE450 cells were transfected with Plko.1-puro-GFP-shRNA-Fat1 plasmid and real time polymerase chain reaction (PCR) was used to verify the efficiency of Fat1 knockdown. The effects of Fat1 and extracellular regulated protein kinase (ERK) pathway inhibitor U0126 on the proliferation of ESCC cells were detected by methyl thiazolyl tetrazolium (MTT). Colony formation assay was used to detect the colony formation ability. Cell cycle was detected by live cell imaging. Western blot was used to observe the level of target protein. Mouse xenograft assay was applied to detect the effect of Fat1 knockdown on KYSE450 cell tumor growth. Immunohistochemistry was used to detect the expressions of related proteins in tumor sections. Results: The efficiency of Fat1 knockdown was (77.1±6.9)% in Fat1 sh1 group and (77.7±7.1)% in Fat1sh2 group. Compared with the control group, the cell proliferation and the expression of p-ERK1/2 were significantly increased in Fat1 sh1 and Fat1sh2 group (P<0.05). After U0126 treatment, the effect of Fat1 knockdown on the proliferation of KYSE450 cells disappeared, and the expression of p-ERK1/2 in KYSE450 cells decreased to a level similar to that in the control group. The number of cell clones in the control group was (72±8), lower than (155±28) and (193±9) in the Fat1sh1 and Fat1sh2 groups, respectively (P<0.05). In KYSE450 cell, division time was shortened from 1 622±32 min in control group to 1 408±29 min in Fat1 sh1 group, the difference was statistically significant (P<0.05). Compared with the control group, the tumor volume of Fat1 knockdown group increased significantly. The tumor weight of control group and Fat1 knockdown group were (0.224±0.028) g and (1.532±0.196) g, respectively, at 4 weeks after inoculation, and the difference was statistically significant (P<0.05). Conclusion: Fat1 inhibits cell proliferation via ERK signaling in ESCC.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Animais , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Camundongos , Transdução de SinaisRESUMO
OBJECTIVE: To investigate the association between educational attainment and the onset of disability in activities of daily living (ADL), and to explore the mediating effect of social participation on such association. METHODS: A longitudinal dataset was drawn from the China Health and Retirement Longitudinal Study (CHARLS, 2015 to 2018). The measurements of educational attainment, social participation and other covariates were identified from 2015, while the outcome measurement of ADL disability was constructed with data from survey 2018. Descriptive analyses were conducted, and basic characteristics and social engagement of the respondents were compared between illiterates and non-illite-rates using Chi-square test. Logistic regression was used to investigate the associations of educational attainment and social participation on the onset of ADL disability. Mediation analysis was employed to examine the mediator role of the social participation on the linkage from being illiterate to the ADL disability onset. RESULTS: A total of 11 359 adults aged 45 years and above were included in the sample, of whom 3 222 were illiterates. The incidence of the onset of ADL disability of illiterates and non-illiterates were 10.4% and 6.2%, respectively. Among these respondents, only half of them were involved in social activities. Of all the 8 social activities, the percentage of interacting with friends (34. 1%) was the highest, and the lowest percentage was observed in participating in an educational or training course (0.6%). Moreover, the percentages of participation in all these 8 social activities among illiterates were significantly lower than that of their educated counterparts (all P < 0.001). The illiterate middle-aged and older adults were less likely to develop ADL disability in the follow-up period [adjusted odds ratio (aOR)=1.22, 95%CI: 1.02-1.45], and social participation was significantly associated with ADL disability onset (aOR=0.73, 95%CI: 0.63-0.85). Findings from mediation analysis illustrated that social participation accounted for 12.22% of the adverse effect of being illiterate on ADL disability onset. CONCLUSION: Social participation could buffer the negative effect of being illiterate on ADL disability onset in middle-aged and older adults, suggesting that engagement in social activities might have impact on prevention of impairments in physical function, especially for middle-aged and older illiterates.
Assuntos
Atividades Cotidianas , Pessoas com Deficiência , Idoso , China/epidemiologia , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Participação SocialRESUMO
In this assay, we developed and evaluated a multiplex PCR (mPCR) for its ability in detecting multiple infections of swine simultaneously. Four pairs of primers were used to detect five viruses. Specific primers were designed for classical swine fever virus (CSFV), African swine fever virus (ASFV) and pseudorabies (PRV). A pair of primers was designed prudently for two different types of porcine reproductive and respiratory syndrome virus that respectively were porcine reproductive and respiratory syndrome virus (PRRSV), highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). The detection limits of the mPCR were 1.09 × 104, 1.50 × 10³, 2.10 × 10³, 1.30 × 10³ and 8.97 × 10² copies/reaction for CSFV, ASFV, HP-PRRSV, PRRSV and PRV, respectively. A total of 49 clinical specimens were tested by the mPCR, and the result showed that co-infection by two or three viruses was 51%. In conclusion, the PCR is a useful tool for clinical diagnosis of not only single infections but also mixed infections in swines.
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Vírus da Febre Suína Africana/isolamento & purificação , Vírus da Febre Suína Clássica/isolamento & purificação , Herpesvirus Suídeo 1/isolamento & purificação , Reação em Cadeia da Polimerase/veterinária , Vírus da Síndrome Respiratória e Reprodutiva Suína/isolamento & purificação , Doenças dos Suínos/virologia , Viroses/veterinária , Animais , Reação em Cadeia da Polimerase/métodos , Vírus da Síndrome Respiratória e Reprodutiva Suína/patogenicidade , Sensibilidade e Especificidade , Suínos , Doenças dos Suínos/diagnóstico , Virulência , Viroses/diagnóstico , Viroses/virologiaRESUMO
The pseudospectral time-domain method has long been used to describe the acoustical wave propagation. However, due to the limitation and difficulties of the fast Fourier transform (FFT) in dealing with nonperiodic problems, the dispersion error is inevitable and the numerical accuracy greatly decreases after the waves arrive at the boundary. To resolve this problem, the Lagrange-Chebyshev interpolation polynomials were used to replace the previous FFT, which, however, brings in an additional restriction on the time step. In this paper, a mapped Chebyshev method is introduced, providing the dual benefit of preserving the spectral accuracy and overcoming the time step restriction at the same time. Three main issues are addressed to assess the proposed technique: (a) Spatial derivatives in the system operator and the boundary treatment; (b) parameter selections; and (c) the maximum time step in the temporal operator. Furthermore, a numerical example involving the time-domain evolution of wave propagation in a duct structure is carried out, with comparisons to those obtained by Euler method, the fourth-order Runge-Kutta method, and the exact analytical solution, to demonstrate the numerical performance of the proposed technique.
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The acoustical wave propagator technique is applied to study the time-domain dynamic stress concentration in a two-dimensional flexible plate with a sharp change of section. As a wave packet approaches the plate discontinuity where the sharp change of thickness is introduced, the spatial interference patterns in the displacement of the plate and internal stresses vary with time. The constructive interference of stresses is referred to as time-domain stress concentration. The superposition of wave fronts of incident and reflected wave packets is used to explain the spatial distribution of the interference patterns. The increase of dynamic stress near the vicinity of the discontinuity boundary of the plate is studied as a function of time and the thickness ratio of the plates.
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In this paper, an explicit acoustical wave propagator technique is introduced to describe the time-domain evolution of acoustical waves in two-dimensional plates. A combined scheme with Chebyshev polynomial expansion and fast Fourier transformation is used to implement the operation of the acoustical wave propagator. Through this operation, the initial wave packet at t = 0 is mapped into the wave packet at any instant t > 0. By comparison of the results of the exact analytical solution and the Euler numerical method, we find that this new Chebyshev-Fourier scheme is highly accurate and computationally effective in predicting the acoustical wave propagation in thin plates. This method offers an opportunity for future study of dynamic stress concentration and time-domain energy flow in coupled structures.
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The voltage-dependent anion-selective channel (VDAC) of the mitochondrial outer membrane is formed by a small (approximately 30 kDa) polypeptide, but shares with more complex channels the properties of voltage-dependent gating and ion selectivity. Thus, it is a useful model for studying these properties. The molecular biology techniques available in yeast allow us to construct mutant versions of the cloned yeast VDAC gene in vitro, using oligonucleotide-directed mutagenesis, and to express the mutant genes in yeast cells in the absence of wild-type VDAC. We find that one substitution mutation (lys 61 to glu) alters the selectivity of VDAC.
Assuntos
Proteínas de Membrana/genética , Porinas , Sequência de Aminoácidos , Canais Iônicos/metabolismo , Canais Iônicos/ultraestrutura , Proteínas de Membrana/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Dados de Sequência Molecular , Mutação , Neurospora crassa/genética , Saccharomyces cerevisiae/genética , Canais de Ânion Dependentes de VoltagemRESUMO
The initial desertification in the Asian interior is thought to be one of the most prominent climate changes in the Northern Hemisphere during the Cenozoic era. But the dating of this transition is uncertain, partly because desert sediments are usually scattered, discontinuous and difficult to date. Here we report nearly continuous aeolian deposits covering the interval from 22 to 6.2 million years ago, on the basis of palaeomagnetic measurements and fossil evidence. A total of 231 visually definable aeolian layers occur as brownish loesses interbedded with reddish soils. This new evidence indicates that large source areas of aeolian dust and energetic winter monsoon winds to transport the material must have existed in the interior of Asia by the early Miocene epoch, at least 14 million years earlier than previously thought. Regional tectonic changes and ongoing global cooling are probable causes of these changes in aridity and circulation in Asia.