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In order to realize in situ multi-frame framing, this paper designed and developed a large-waist framing converter tube. The size ratio between the waist and the object was about 1.16:1. The subsequent test results showed that the static spatial resolution of the tube could reach 10 lp/mm (@ 72.5%) under the premise of this adjustment, and the transverse magnification could reach 2.9. Once the MCP (Micro Channel Plate) traveling wave gating unit is equipped at the output end, it is expected to promote the further development of in situ multi-frame framing technology.
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The development of inertial confinement fusion (ICF) experiments necessitates the diagnostic instrument to have multiple frames with a high spatial and temporal resolution for the two-dimensional detection of the hot spot at the implosion end of the ICF. The existing sampling two-dimensional imaging technology in the world has superior performance; however, its subsequent development requires a streak tube with large lateral magnification. In this work, an electron beam separation device was designed and developed for the first time. The device can be used without changing the structure of the streak tube. It can be combined directly with the corresponding device and matched with a special control circuit. Based on the original transverse magnification, 1.77 times the secondary amplification can be achieved, which is conducive to expanding the recording range of the technology. The experimental results showed that the static spatial resolution of the streak tube after the inclusion of the device can still reach 10 lp/mm.
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For an electron-optical imaging system with wide beam focusing, the calculation of the field curvature can be performed only theoretically and requires the specific analytical expressions of the axial potential distribution in the streak tube and its corresponding derivatives, making the calculation cumbersome. Even when the electron trajectory is tracked using the numerical calculation method, the calculated results cannot be verified experimentally. A method for measuring the field curvature of the streak tube based on the spherical fluorescent screen is proposed for the first time, to the best of our knowledge. This method can directly measure the field curvature from the experimental image without requiring information on the internal structure of the streak tube, which is extremely useful for the design of the subsequent image reconstruction algorithm.
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Doxorubicin (DOX) is a potent anti-neoplastic agent with cumulative cardiotoxicity. DOX-induced cardiotoxicity has been shown to depend on the different dosing times. However, the basis for determining the dosing time to minimize DOX-induced cardiotoxicity and the underlying mechanisms remain incompletely understood. Here we first showed that SIRT3, the major mitochondrial deacetylase, is negatively correlated to DOX-induced cardiotoxicity through the regulation of ATP production, mitochondrial membrane potential (MMP) level and ROS level in human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Then, we used in vivo experiments to demonstrate that DOX significantly reduced the SIRT3 expression and the SIRT3 activity as reflected by the increased AcK68MnSOD/MnSOD ratio in rats after six weeks of treatment. Notably, the activity of SIRT3 had an obvious diurnal rhythm pattern in the myocardium of healthy rats. More importantly, an obvious lower AcK68MnSOD/MnSOD ratio was observed in rat hearts with DOX administrated at Zeitgeber time (ZT) 9 (ZT 0 was the time lights were turned on) than ZT1, which represent the peak and trough of SIRT3 activity. Moreover, DOX ZT9 reduced the body weight loss, extended the survival period, improved the heart function and alleviated the myocardial lesions compared to DOX ZT1. Mechanistic investigations demonstrated that DOX ZT1 significantly reduced ATP production, oxygen consumption rate (OCR) at various respiration states, MMP level and MnSOD activity and enhanced the H2O2 level compared with CON ZT1, whereas there was no significant effect for DOX ZT9 compared with CON ZT9. Taken together, dosing at the peak time of SIRT3 activity reduced DOX-induced cardiotoxicity, which may be related to the increased endogenous tolerance against the mitochondrial dysfunction and oxidative stress caused by DOX.
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Antibióticos Antineoplásicos/efeitos adversos , Cardiotoxicidade/prevenção & controle , Doxorrubicina/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Sirtuína 3/metabolismo , Animais , Antibióticos Antineoplásicos/administração & dosagem , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Cardiotoxicidade/patologia , Linhagem Celular , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos Sprague-DawleyRESUMO
In this paper, a novel method using the modified Langmuir-Blodgett and float-transfer techniques was introduced to construct the perfect PS monolayer nanosphere template with large area up to cm(2). Based on such templates, the diameter, length, packing density, and the shape of Si nanopillar arrays (Si NPAs) could be precisely controlled and tuned through the modified nanosphere lithography combined with a metal-assisted chemical etching (NSL-MACE) method. Manipulation of the etching time can effectively avoid permanent deformation/clumping to generate size-tunable Si NPAs. The optical properties of the Si NPAs can be controlled by the Si NPA morphologies resulting from the different reactive ion etching (RIE) time and chemical etching time. The enhanced antireflective property and electromagnetic field effect of Au/Si NPAs were proved by the results. The new modified NSL-MACE technique with the capability of scale-up fabrication of Si NPAs would be helpful for potential applications in optoelectronic devices.
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Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 50 genes. To identify genetic mutations underlying autosomal recessive RP (arRP), we performed whole-exome sequencing study on two consanguineous marriage Indian families (RP-252 and RP-182) and 100 sporadic RP patients. Here we reported novel mutation in FAM161A in RP-252 and RP-182 with two patients affected with RP in each family. The FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. By whole-exome sequencing we identified several homozygous genomic regions, one of which included the recently identified FAM161A gene mutated in RP28-linked arRP. Sequencing analysis revealed the presence of a novel homozygous frameshift mutation p.R592FsX2 in both patients of family RP-252 and family RP-182. In 100 sporadic Indian RP patients, this novel homozygous frameshift mutation p.R592FsX2 was identified in one sporadic patient ARRP-S-I-46 by whole-exome sequencing and validated by Sanger sequencing. Meanwhile, this homozygous frameshift mutation was absent in 1000 ethnicity-matched control samples screened by direct Sanger sequencing. In conclusion, we identified a novel homozygous frameshift mutations of RP28-linked RP gene FAM161A in Indian population.
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Exoma , Proteínas do Olho/genética , Mutação da Fase de Leitura , Homozigoto , Linhagem , Retinose Pigmentar/genética , Feminino , Genes Recessivos , Estudo de Associação Genômica Ampla , Humanos , Índia , MasculinoRESUMO
The changes in protein degradation (TCA-soluble peptides), Schiff bases, dicarbonyl compounds (glyoxal-GO, methylglyoxal-MGO) and two typical advanced glycation end-products (AGEs) including Nε-carboxymethyllysine (CML), Nε-carboxyethyllysine (CEL) levels in ground pork supplemented with sucrose (4.0%) were investigated under nine freeze-thaw cycles and subsequent heating (100 °C/30 min). It was found that increase in freeze-thaw cycles promoted protein degradation and oxidation. The addition of sucrose further promoted the production of TCA-soluble peptides, Schiff bases and CEL, but not significantly, ultimately leading to higher levels of TCA-soluble peptides, Schiff bases, GO, MGO, CML, and CEL in the ground pork with the addition of sucrose than in the blank groups by 4%, 9%, 214%, 180%, 3%, and 56%, respectively. Subsequent heating resulted in severe increase of Schiff bases but not TCA-soluble peptides. Contents of GO and MGO all decreased after heating, while contents of CML and CEL increased.
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The influences of frozen-then-chilled storage of minced pork on the formation of advanced glycation end-products (AGEs) including Nε-carboxymethyllysine and Nε-carboxyethyllysine, and their corresponding α-dicarbonyl precursors (α-DPs; glyoxal and methylglyoxal) during storage and subsequent heating were investigated in comparison with chilled storage. During cold storage, the levels of AGEs, trichloroacetic acid-soluble peptides, and Schiff bases in minced pork continuously increased while α-DPs decreased. The 30 min heating (100 °C) resulted in 64-560% increase of AGEs in pork, corresponding with an increase of Schiff bases and decreases of α-DPs. Compared to the chilled storage, the frozen-then-chilled storage led to no significant difference (P > 0.05) on the levels of AGEs and α-DPs in raw or heat-treated pork, implying that the formation and thawing of ice crystals in pork during the frozen-then-chilled storage had minor to no effects on the formation of AGEs and their α-DPs.
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Carne de Porco , Carne Vermelha , Animais , Suínos , Carne Vermelha/análise , Reação de Maillard , Bases de Schiff , Calefação , Produtos Finais de Glicação Avançada/químicaRESUMO
The contents of free and protein-bound advanced glycation end-products (AGEs) including Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL), along with glyoxal (GO), methylglyoxal (MGO), chemical components, and salt in commercially prepared and prefabricated fish products were analyzed. Snack food classified as commercially prepared products exhibited higher levels of GO (25.00 ± 3.34-137.12 ± 25.87 mg/kg of dry matter) and MGO (11.47 ± 1.39-43.23 ± 7.91 mg/kg of dry matter). Variations in the contents of free CML and CEL increased 29.9- and 73.0-fold, respectively. Protein-bound CML and CEL in commercially prepared samples were higher than those in raw prefabricated ones due to the impact of heat treatment. Levels of GO and MGO demonstrated negative correlations with fat (R = -0.720 and -0.751, p < 0.05) in commercially prepared samples, whereas positive correlations were observed (R = 0.526 and 0.521, p < 0.05) in raw prefabricated ones. The heat-induced formation of protein-bound CML and CEL showed a negative correlation with the variations of GO and MGO but was positively related to protein levels in prefabricated products, suggesting that GO and MGO may interact with proteins to generate AGEs during heating. The influence of NaCl on the formation of GO and MGO exhibited variations across different fish products, necessitating further investigation.
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This study aimed to evaluate the effects of lactic acid (LA), citric acid (CA), and malic acid (MA) varying in concentration (0.5−2.0% w/w) on the rheological properties of fish gelatin (1.5−6.67% w/w) obtained from the skin of tilapia (Oreochromis mossambicus). The addition of LA, CA, or MA in gelatin dispersions significantly (p < 0.05) weakened their gel strengths, leading to a 14.3−62.2 reduction in gel strength. The gel strength, elastic (G'), and viscous (Gâ³) moduli, as well as the gelling (TG) and melting (TM) temperatures of gelatin dispersions decreased with an increased level of acid added, implying the weakening effects of these acids on junction zones of the gelatin network in aqueous media. The addition of LA had less effect on these rheological properties of gelatin dispersions as compared to that of MA and CA, which were consistent with their effects on the pH of gelatin dispersions. Moreover, the reductions of TG and TM for gelatin dispersions with a higher gelatin concentration (e.g., 6.67% gelatin with 0.5% LA, TG dropped 0.4 °C) due to the addition of LA, CA, or MA were less pronounced compared to those with a lower gelatin content (e.g., 2% gelatin with 0.5% LA, TG dropped 7.1 °C), likely attributing to the stronger buffering effect of the high gelatin dispersion and less percentage reduction in the junction zones in the dispersion due to the addition of an acid. Incorporation of the effects of acids on the linear relationships (R2 = 0.9959−0.9999) between the square of gelatin concentrations and G' or Gâ³ could make it possible to develop a model to predict G', Gâ³, phase transition temperatures of gelatin dispersions containing different amounts of gelatin and acid (within the tested range) in the future.
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Lipid oxidation and protein degradation, along with the formation of advanced glycation end-products (AGEs), including Nε-carboxymethyl-lysine (CML), Nε-carboxyethyl-lysine (CEL) and fluorescent AGEs, in raw and subsequently heated surimi products were investigated during freezing-thawing cycles. Lipid oxidation, protein degradation, Schiff base, and AGEs formation constantly increased during freezing-thawing cycles and heat treatment (P < 0.05). Heat-induced increase of AGEs in surimi products was accelerated by freezing-thawing treatment. Formation of CML in one-stage heated (45 °C, 30 min) samples increased from 0.10 ± 0.04 to 0.53 ± 0.11 mg/kg and CEL increased from 0.03 ± 0.32 to 0.92 ± 0.74 mg/kg. In two-stage heated samples (45 °C, 30 min and 90 °C, 20 min), CML increased from 0.86 ± 0.06 to 1.12 ± 0.11 mg/kg and CEL from 1.00 ± 0.34 to 2.11 ± 1.86 mg/kg, during up to 6 freezing-thawing cycles. Formation of fluorescent AGEs derived from heating was also significantly accelerated by freezing-thawing treatment (P < 0.01). Correlation analysis suggested that the chemical synthesis of AGEs in surimi products was promoted by lipid oxidation and protein degradation during freezing-thawing cycles. AGEs formation through Schiff base oxidation likely occurred only under thermal treatment since no relationship was found between Schiff base and AGEs levels in raw surimi products.
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Carpas , Produtos Finais de Glicação Avançada , Animais , Carpas/metabolismo , Congelamento , Produtos Finais de Glicação Avançada/análise , Temperatura Alta , Lipídeos , Bases de SchiffRESUMO
Programmed necrosis is a new modulated cell death mode with necrotizing morphological characteristics. Receptor interacting protein 1 (RIPK1) is a critical mediator of the programmed necrosis pathway that is involved in stroke, myocardial infarction, fatal systemic inflammatory response syndrome, Alzheimer's disease, and malignancy. At present, the reported inhibitors are divided into four categories. The first category is the type I ATP-competitive kinase inhibitors that targets the area occupied by the ATP adenylate ring; The second category is type â ¡ ATP competitive kinase inhibitors targeting the DLG-out conformation of RIPK1; The third category is type â ¢ kinase inhibitors that compete for binding to allosteric sites near ATP pockets; The last category is others. This paper reviews the structure, biological function, and recent research progress of receptor interaction protein-1 kinase inhibitors.
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Intermittent hypoxia (IH) is the core pathological feature of obstructive sleep apnea syndrome (OSAS), and insulin resistance (IR) is the most common metabolic complication of OSAS. Studies have shown that the levels of free fatty acids (FFAs), which are mainly released from adipocytes by lipolysis, are elevated in OSAS and play an important role in the development of IR. However, whether and how IH regulates adipocyte lipolysis in OSAS is not clear. Here, we revealed that the apnea hypopnea index was positively correlated with the serum levels of FFAs and FFA release from adipocytes in OSAS. In addition, IH facilitated lipolysis and FFA release from adipocytes by downregulating the level of METTL3. METTL3 downregulation impaired N6-methyladenosine (m6A) levels in MGLL mRNA and reduced MGLL expression, thereby promoting lipolysis. In addition, we identified YTHDF2 as the m6A reader that interacts with MGLL mRNA, accelerating its degradation. Furthermore, our data showed reduced levels of METTL3 and elevated levels of MGLL in the adipose tissues of OSAS patients and indicated an effect of METTL3 on lowering FFA levels and improving IR in rats with chronic IH. In conclusion, our study provides new insights into the development and treatment of IR in OSAS.
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The absorption, fluorescence, and transient absorption spectra of Tetra(alpha-amino) zinc phthalocyanine, ZnPc(alpha-NH2)4, have been measured in polar solvents and compared with that of ZnPc(alpha-R)4 (R = H, NO2, OCH(CH3)2). While the latter three showed the typical photophysics of phthalocyanines, ZnPc(alpha-NH2)4 exhibits distinct spectral properties, a very low fluorescence quantum yield and a relatively long fluorescence lifetime. These observations are explained by the substantial charge transfer characters in the absorption and fluorescence spectra of ZnPc(alpha-NH2)4. NMR indicates that intramolecular H-bonding makes atoms in NH2 actually coplanar with other elements of ZnPc(alpha-NH2)4. The local excited state is non emissive and the weak emission is assigned to its charge transfer state. The transient absorption bands from laser flash photolysis located at 630 nm, 645 nm is assigned to the mono-charge transfer state, while that at 545 nm is assigned to the di-charge transfer state.
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The photoresponsive J-aggregation behaviors of a novel azobenzene-substituted zinc phthalocyanine (azo-ZnPc dyad) were studied by UV/vis, fluorescence, and (1)H NMR spectroscopy. Upon illumination with 365 nm UV light, the trans-cis isomerization of azobenzene can efficiently reduce the steric hindrance around the peripheral oxygen atom of azo-ZnPc, shortening the possible distance between two phthalocyanine molecules and, consequently, greatly improving the tendency of J-aggregation of azo-ZnPc dyad. The third-order optical nonlinearities of the photoresponsive J-aggregates (before and after illumination) were measured by a Z-scan technique at 532 nm with a pulse duration of 25 ps. The Z-scan spectra revealed that all the samples possessed large positive nonlinear refraction and positive nonlinear absorption, exhibiting a self-focusing effect and reverse saturable absorption, respectively. The second molecular hyperpolarizabilities of the dyad in two conditions were measured to be 3.87 x 10(-30) and 4.82 x 10(-30) esu, respectively. All the results suggest that the azo-ZnPc dyad has potential in the field of nonlinear optics applications.
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The effects of cold storage (0⯰C, 0-8â¯days) and salts (NaCl, 0.5-5%; NaNO2, 50-150â¯mg/kg) on the formation of protein-bound NÉ-(carboxymethyl)lysine (CML) and NÉ-(carboxyethyl)lysine (CEL) in raw and subsequently commercially sterilized (121⯰C, 10â¯min) pork were investigated. Based upon two-factor analysis of variance (αâ¯=â¯0.05), there was no significant interaction effect between salts and storage time on the levels of CML and CEL in raw or sterile pork; salts and storage time did not significantly affect the amounts of CML and CEL in raw pork. However, in sterile pork, 1.5-5% NaCl treatments led to an average of 7.5-52.6% increase in CML, while NaNO2 resulted in 25.4-37.1% and 21.4-23.4% reduction in CML and CEL, respectively; raw pork stored for 8â¯days led to 82.5% increase of CML and 32.6% increase of CEL in the sterile products (nâ¯=â¯30), as compared to those without cold storage.
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Cromatografia Líquida de Alta Pressão , Lisina/análogos & derivados , Carne Vermelha/análise , Sais/química , Espectrometria de Massas em Tandem , Animais , Produtos Finais de Glicação Avançada/análise , Lisina/análise , Proteínas/análise , Proteínas/química , Esterilização , Suínos , Temperatura , Fatores de TempoRESUMO
Surface plasmon resonance (SPR) nanosensors based on metallic nanohole arrays have been widely reported to detect binding interactions in biological specimens. A simple and effective method for constructing nanoscale arrays is essential for the development of SPR nanosensors. In this work, we report a one-step method to fabricate nanohole arrays by thermal nanoimprinting in the matrix of IPS (Intermediate Polymer Stamp). No additional etching process or supporting substrate is required. The preparation process is simple, time-saving and compatible for roll-to-roll process, potentially allowing mass production. Moreover, the nanohole arrays were integrated into detection platform as SPR sensors to investigate different types of biological binding interactions. The results demonstrate that our one-step method can be used to efficiently fabricate large-area and uniform nanohole arrays for biochemical sensing.
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Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Ouro/química , Nanoestruturas/química , Nanotecnologia/instrumentação , Ressonância de Plasmônio de Superfície , Modelos Químicos , Nanoestruturas/ultraestrutura , Ligação ProteicaRESUMO
An eight-frame gated microchannel plate (MCP) camera and a gating electrical pulse are described in this article. The gating electrical pulse is obtained by first generating a high voltage fast step pulse using avalanche transistors in Marx bank configuration, and then shaping it using avalanche diodes. The high voltage fast step pulse is about 200 ps in fall time and 4 kV in amplitude. The gating pulse wave form with width of 160 ps and amplitude of 2.5 kV is achieved. Each frame photocathode coated with gold on the MCP is part of a 12 Omega transmission line with open circuit end driven by the gating electrical pulse. The camera is tested by illuminating its photocathode with ultraviolet laser pulses, 266 nm in wavelength, which shows exposure time as short as 120 ps.
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Intensificação de Imagem Radiográfica/instrumentação , Interpretação de Imagem Radiográfica Assistida por Computador/instrumentação , Processamento de Sinais Assistido por Computador/instrumentação , Campos Eletromagnéticos , Desenho de Equipamento , Análise de Falha de Equipamento , Intensificação de Imagem Radiográfica/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
In this paper, we focused on the large-scale fabrication of gold nanoholes array capable of supporting surface plasmonic resonance (SPR) via the developed nanosphere lithography (NSL) technique, which could be used as high performance biosensor for the detection of specific streptavidin-biotin interactions. Direct UV-vis absorption mode measurement was used to monitor the SPR peak shift. For the better immobilization of biotin, the surface of gold nanoholes array was functionalized with 3-mercaptopropyl trimethoxysilane (MPTS) and 3-aminopropyl triethoxysilane (APTES). After the streptavidin binding to the biotin, the SPR peak position showed an 11 nm wavelength shift due to the refractive index change caused by the biotin-streptavidin binding. The sealing treatment was performed by using bovine serum albumin (BSA) to eliminate the influences of nonspecific adsorption for more accurate detection. Interestingly, the detection sensitivity of the gold nanoholes array could be further enhanced by coupling the water-soluble CdSe/ZnS quantum dots (QDs), which showed four-fold improvement in detection sensitivity as compared to the gold nanoholes array biosensor without the coupling of QDs. The mechanisms for the enhancement of detection sensitivity were also discussed. This would provide new capabilities for the highly sensitive measurements of biomolecular binding.
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Ouro/química , Nanoestruturas/química , Pontos Quânticos/química , Animais , Biotina/química , Bovinos , Vidro/química , Nanoestruturas/ultraestrutura , Soroalbumina Bovina/química , Estreptavidina/química , Ressonância de Plasmônio de Superfície/métodosRESUMO
A novel family of thiophene-decorated phthalocyanines (M-TPcs) was efficiently synthesized, during which the key intermediate of these compounds was purified through a chemical approach. In the optimized geometries of M-TPcs, the peripherally linked thiophene rings are tilted from the Pc core, which oppose aggregation considering the mutual steric hindrance. However, Zn-TPc formed J-aggregates in many solvents while Ni-TPc and Cu-TPc did not. Octaphenyl-substituted zinc Pc (Zn-PPc) showed similar J-aggregation behavior as Zn-TPc. This unusual J-aggregation was attributed to the conformational planarization of the corresponding molecules.