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Vascular calcification is frequently seen in patients with chronic kidney disease (CKD), and significantly increases cardiovascular mortality and morbidity. Sirt7, a NAD+-dependent histone deacetylases, plays a crucial role in cardiovascular disease. However, the role of Sirt7 in vascular calcification remains largely unknown. Using in vitro and in vivo models of vascular calcification, this study showed that Sirt7 expression was significantly reduced in calcified arteries from mice administered with high dose of vitamin D3 (vD3). We found that knockdown or inhibition of Sirt7 promoted vascular smooth muscle cell (VSMC), aortic ring and vascular calcification in mice, whereas overexpression of Sirt7 had opposite effects. Intriguingly, this protective effect of Sirt7 on vascular calcification is dependent on its deacetylase activity. Unexpectedly, Sirt7 did not alter the osteogenic transition of VSMCs. However, our RNA-seq and subsequent studies demonstrated that knockdown of Sirt7 in VSMCs resulted in increased intracellular reactive oxygen species (ROS) accumulation, and induced an Nrf-2 mediated oxidative stress response. Treatment with the ROS inhibitor N-acetylcysteine (NAC) significantly attenuated the inhibitory effect of Sirt7 on VSMC calcification. Furthermore, we found that knockdown of Sirt7 delayed cell cycle progression and accelerated cellular senescence of VSMCs. Taken together, our results indicate that Sirt7 regulates vascular calcification at least in part through modulation of ROS and cellular senescence of VSMCs. Sirt7 may be a potential therapeutic target for vascular calcification.
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Senescência Celular , Músculo Liso Vascular , Miócitos de Músculo Liso , Estresse Oxidativo , Espécies Reativas de Oxigênio , Sirtuínas , Calcificação Vascular , Animais , Calcificação Vascular/patologia , Calcificação Vascular/metabolismo , Calcificação Vascular/genética , Espécies Reativas de Oxigênio/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Camundongos , Sirtuínas/metabolismo , Sirtuínas/genética , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Masculino , Colecalciferol/farmacologia , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/genética , Camundongos Endogâmicos C57BL , Células CultivadasRESUMO
Atherosclerosis, a chronic inflammatory condition primarily affecting large and medium arteries, is the main cause of cardiovascular diseases. Macrophages are key mediators of inflammatory responses. They are involved in all stages of atherosclerosis development and progression, from plaque formation to transition into vulnerable plaques, and are considered important therapeutic targets. Increasing evidence suggests that the modulation of macrophage polarization can effectively control the progression of atherosclerosis. Herein, we explore the role of macrophage polarization in the progression of atherosclerosis and summarize emerging therapies for the regulation of macrophage polarization. Thus, the aim is to inspire new avenues of research in disease mechanisms and clinical prevention and treatment of atherosclerosis.
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Aterosclerose , Placa Aterosclerótica , Humanos , Aterosclerose/tratamento farmacológico , Macrófagos , ArtériasRESUMO
Ultra-wide slabs have a good application market and prospect, but there is still a lack of research on the flow field. To explore the characteristics of its flow field, this study built a 0.5-scale physical model of mold using Perspex. The effect of casting speed on flow field and surface flow speed was investigated by using an ink tracer experiment and contact measurement. There were various flow patterns in the ultra-wide slab mold, and they continue to transform each other. The jet momentum from the nozzle ports was diffused by colliding with the wide face, which lowered its kinetic energy and affected its subsequent diffusion. Compared with the conventional mold, the upper flow intensity of the ultra-wide slab mold was weaker, which made its liquid surface inactive and caused it to produce a flux rim or slag strip. At different casting speeds, the average flow speed distribution of the ultra-wide slab was C-shaped. When it increased from 0.9 to 1.4 m/s, the corresponding maximum average flow speed increased from 0.08 to 0.2 m/s. At the same time, the proportion of the low-flow speed zone at the most active part of the surface also gradually decreased from more than 90% to about 49%.
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Heavily co-doped Cu2SnS3 can achieve a high power factor by relying on a high electrical conductivity (σ), which subsequently limits the ZT value with a large electronic thermal conductivity (κe). We report here an enhanced ZT for Cu2Sn0.9Co0.1S3 decorated with micro-nanoscale AgSnSe2 along grain boundaries. The AgSnSe2 phase served as a charge carrier filter by ionized impurity scattering, with a noticeable bottoming out of carrier mobility and a rapid increase in the Seebeck coefficient as the temperature increased from 423 to 573 K, which properly reduced the large σ and κe while maintaining a high power factor of approximately 10 µW cm-1 K-2 at 773 K. Lattice thermal conductivity was markedly suppressed, and a low total thermal conductivity was obtained with strengthened phonon scattering by the AgSnSe2 phase as a phonon barrier. With the synergistic effects on electrical and thermal transport, a maximum ZT of 0.93 at 773 K was achieved in Cu2Sn0.9Co0.1S3-3 wt% AgSnSe2.
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Recent studies have shown that short-chain fatty acids (SCFAs), primarily acetate, propionate and butyrate, play a crucial role in the pathogenesis of cardiovascular disease. Whether SCFAs regulate vascular calcification, a common pathological change in cardiovascular tissues, remains unclear. This study aimed to investigate the potential role of SCFAs in vascular calcification. Using cellular and animal models of vascular calcification, we showed that butyrate significantly enhanced high phosphate (Pi)-induced calcification and osteogenic transition of vascular smooth muscle cells (VSMC) in vitro, whereas acetate and propionate had no effects. Subsequent studies confirmed that butyrate significantly promoted high Pi-induced aortic ring calcification ex vivo and high dose vitamin D3 (vD3)-induced mouse vascular calcification in vivo. Mechanistically, butyrate significantly inhibited histone deacetylase (HDAC) expression in VSMCs, and a pan HDAC inhibitor Trichostatin A showed similar inductive effects on calcification and osteogenic transition of VSMCs to butyrate. In addition, the SCFA sensing receptors Gpr41 and Gpr109a were primarily expressed by VSMCs, and butyrate induced the rapid activation of NF-κB, Wnt and Akt signaling in VSMCs. Intriguingly, the NF-κB inhibitor SC75741 significantly attenuated butyrate-induced calcification and the osteogenic gene Msx2 expression in VSMCs. We showed that knockdown of Gpr41 but not Gpr109a attenuated butyrate-induced VSMC calcification. This study reveals that butyrate accelerates vascular calcification via its dual effects on HDAC inhibition and NF-κB activation. Our data provide novel insights into the role of microbe-host interaction in vascular calcification, and may have implications for the development of potential therapy for vascular calcification.
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NF-kappa B , Calcificação Vascular , Animais , Butiratos/metabolismo , Butiratos/farmacologia , Células Cultivadas , Inibidores de Histona Desacetilases/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Camundongos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , NF-kappa B/metabolismo , Fosfatos , Propionatos/metabolismo , Propionatos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Calcificação Vascular/patologia , Vitamina DRESUMO
Solar irradiance has been universally acknowledged to be dominant by quasi-decadal variability, which has been adopted frequently to investigate its effect on climate decadal variability. As one major terrestrial energy source, solar-wind energy flux into Earth's magnetosphere (Ein) exhibits dramatic interannual variation, the effect of which on Earth's climate, however, has not drawn much attention. Based on the Ein estimated by 3D magnetohydrodynamic simulations, we demonstrate a novelty that the annual mean Ein can explain up to 25% total interannual variance of the northern-hemispheric temperature in the subsequent boreal winter. The concurrent anomalous atmospheric circulation resembles the positive phase of Arctic Oscillation/North Atlantic Oscillation. The warm anomalies in the tropic stratopause and tropopause induced by increased solar-wind-magnetosphere energy persist into the subsequent winter. Due to the dominant change in the polar vortex and mid-latitude westerly in boreal winter, a 'top-down' propagation of the stationary planetary wave emerges in the Northern Hemisphere and further influences the atmospheric circulation and climate.
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Increasing greenhouse gas concentration and ozone depletion are generally considered two important factors that affect the variability of the Antarctic Oscillation (AAO). Here, we find that the first leading mode of sea surface temperature (SST) variability (rotated empirical orthogonal functions) shows a long-term upward trend from 1901 to 2004 and is closely related to the AAO index that is obtained using the observationally constrained reanalysis data. Further, regressions of the sea level pressure and the 500-hPa geopotential height anomalies, against the principle component associated with the long-term SST anomalies, display a seesaw behavior between the middle and high latitudes of the Southern Hemisphere in austral winter, which is similar to the high polarity of the AAO. The circulation responses to the long-term oceanic warming in three numerical models are consistent with the observed results. This finding suggests that the long-term oceanic warming is partly responsible for the upward trend of the AAO in austral winter. The thermal wind response to the oceanic warming in South Indian and South Atlantic Ocean may be a possible mechanism for this process.
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BACKGROUND: As drug-eluting stent (DES) has almost overcome the disadvantage of frequent restenosis, off-pump coronary artery bypass grafting (OPCAB) has been introduced to avoid complications of cardiopulmonary bypass. However, which approach may promise better outcomes for patients with coronary artery disease remains controversial. METHODS: Three databases were searched. The outcomes of interest were major adverse cardiac and cerebrovascular events (MACCE), all-cause death, target vessel revascularization (TVR), repeat revascularization (RRV), myocardial infarction (MI), and cerebrovascular events (CVE). The relative risk (RR) was calculated as the summary statistic. RESULTS: 11,452 patients from 22 studies were included, of which 4949 patients underwent OPCAB and 6503 patients received DES. The cumulative rates of MACCE (RR [95% CI]=0.43 [0.34, 0.54], P<0.00001), all-cause death (RR [95% CI]=0.56 [0.33, 0.96], P=0.03), TVR (RR [95% CI]=0.33 [0.21, 0.53], P<0.00001), RRV (RR [95% CI]=0.22 [0.11, 0.42], P<0.00001) and MI (RR [95% CI]=0.13 [0.05, 0.29], P<0.00001) at 3 years were all lower in OPCAB group. The incidences of in-hospital death (RR [95% CI]=1.31 [0.81, 2.13], P=0.27) and MI (RR [95% CI]=1.03 [0.60, 1.78], P=0.92) were not different between groups, but the rate of in-hospital CVE was lower (RR [95% CI]=2.6355 [1.0033, 6.9228], P=0.05) in DES group. CONCLUSIONS: OPCAB presents better long-term outcomes of MACCE, all-cause mortality, TVR, RRV and MI but uncertain outcome of postoperative CVE without influencing the incidences of in-hospital death and MI.
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Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Humanos , Resultado do TratamentoRESUMO
OBJECTIVE: To prepare the polyclonal antibody against methyl-accepting chemotaxis signal transduction protein (MCP) of Helicobacter hepaticus (H.hepaticus). METHODS: The recombinant plasmid pET22b+/MCP was transformed into E.coli BL2l(DE3) to express the fusion protein His-rhMCP under the induction of IPTG. The fusion protein was purified and the antibody was obtained by immunizing rabbits. The titer of the polyclonal antibody was tested by indirect ELISA, and the specificity of the antibody was identified based on Western blotting using the prepared cell surface proteins (CSPs) of the bacteria. RESULTS: The fusion protein was successfully expressed, and the titer of the antibody reached 1:32 000. Western blotting indicated that the antibody could specifically bind to CSPs and His-rhMCP. CONCLUSION: The antibody with a high titer and specificity was prepared to facilitate further study of the pathogenicity and epidemiology of H.hepaticus in human.
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Anticorpos Antibacterianos/biossíntese , Helicobacter hepaticus/imunologia , Proteínas Recombinantes de Fusão/biossíntese , Animais , Anticorpos Antibacterianos/genética , Especificidade de Anticorpos , Proteínas de Bactérias/imunologia , Helicobacter hepaticus/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Coelhos , Proteínas Recombinantes de Fusão/genética , Transdução de SinaisRESUMO
OBJECTIVE: To analyze the clinical manifestations, epidemiological features, pathogens, treatment and outcomes of 112 patients with infectious endocarditis. METHODS: The clinical data were reviewed for all the patients with the diagnosis of infectious endocarditis in Nanfang Hospital over the period from 2002 to 2012. RESULTS: The average age of disease onset was 46∓17.1 years among these cases. Seventy patients (62.5%) had underlying cardiac conditions, including, in the order of frequency, rheumatic heart disease, congenital cardiovascular anomalies, and senile valve degeneration. Clinically the patients presented with fever, anemia, congestive heart failure, and embolism events, etc. Echocardiography found endocardial neoplasms in 105 cases, and the mitral valve was often involved. Blood culture yielded positive results in 61 cases, and the most common causative bacteria were Streptococcus (20.5%), Staphylococcus (19.6%) and Enterococcus (5.4%). Surgical intervention was performed in 78 cases. Ninety-one patients were cured or improved after comprehensive treatment, and 10 discontinued treatment for financial reasons; 11 died of cardiac failure (8 cases), pulmonary embolism (2 cases) and central nervous system events (1 case). CONCLUSION: Infectious endocarditis shows a significant change in the clinical profiles and its mortality remains high despite improved diagnostic and therapeutic procedures.
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Endocardite Bacteriana , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Endocardite Bacteriana/epidemiologia , Endocardite Bacteriana/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
In the continuous casting of steel, mold fluxes play an important role in improving surface quality of casting strands and maintaining the continuous casting process. The physiochemical property of mold fluxes is definitely correlated with the microstructure. Fluorides play an important role in modifying the high temperature properties of mold fluxes. So, studying the effect of fluoride on multicomponent silicate structure is helpful to understanding the performance of fluoride in mould fluxes. In the present paper, effects of fluorine on melt, glass and crystal structure of silicate were studied by using Raman spectroscopy and in situ high temperature technique. The results were as follows: While the content of CaF2 increased, the varieties and relative quantities of microstructural units of silicates changed, the polymerization of the silicate network decreased, and the viscosity of the melt decreased; comparing non-fluoride with high-fluorine mold fluxes, the main kind of microstructure of silicates in mold fluxes with high fluorine was mostly monomer, while in fluorine free mold fluxes it was mainly chain of microstructure. It would help to develop fluorine free mold fluxes.