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Diabetic retinopathy (DR) is a very serious diabetes complication. Changes in the O-linked N-acetylglucosamine (O-GlcNAc) modification are associated with many diseases. However, its role in DR is not fully understood. In this research, we explored the effect of O-GlcNAc modification regulation by activating AMP-activated protein kinase (AMPK) in DR, providing some evidence for clinical DR treatment in the future. Bioinformatics was used to make predictions from the database, which were validated using the serum samples of diabetic patients. As an in vivo model, diabetic mice were induced using streptozotocin (STZ) injection with/without an AMPK agonist (metformin) or an AMPK inhibitor (compound C) treatment. Electroretinogram (ERG) and H&E staining were used to evaluate the retinal functional and morphological changes. In vitro, 661 w cells were exposed to high-glucose conditions, with or without metformin treatment. Apoptosis was evaluated using TUNEL staining. The protein expression was detected using Western blot and immunofluorescence staining. The angiogenesis ability was detected using a tube formation assay. The levels of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) in the serum changed in the DR patients in the clinic. In the diabetic mice, the ERG wave amplitude and retinal thickness decreased. In vitro, the apoptotic cell percentage and Bax expression were increased, and Bcl2 expression was decreased in the 661 w cells under high-glucose conditions. The O-GlcNAc modification was increased in DR. In addition, the expression of GFAT/TXNIP O-GlcNAc was also increased in the 661 w cells after the high-glucose treatment. Additionally, the Co-immunoprecipitation(CO-IP) results show that TXNIP interacted with the O-GlcNAc modification. However, AMPK activation ameliorated this effect. We also found that silencing the AMPKα1 subunit reversed this process. In addition, the conditioned medium of the 661 w cells may have affected the tube formation in vitro. Taken together, O-GlcNAc modification was increased in DR with photoreceptor cell degeneration and neovascularization; however, it was reversed after activating AMPK. The underlying mechanism is linked to the GFAT/TXNIP-O-GlcNAc modification signaling axis. Therefore, the AMPKα1 subunit plays a vital role in the process.
Assuntos
Proteínas Quinases Ativadas por AMP , Acetilglucosamina , Diabetes Mellitus Experimental , Retinopatia Diabética , N-Acetilglucosaminiltransferases , Retinopatia Diabética/metabolismo , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/patologia , Animais , Camundongos , Acetilglucosamina/metabolismo , N-Acetilglucosaminiltransferases/metabolismo , N-Acetilglucosaminiltransferases/antagonistas & inibidores , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Masculino , Apoptose/efeitos dos fármacos , Metformina/farmacologia , beta-N-Acetil-Hexosaminidases/metabolismo , beta-N-Acetil-Hexosaminidases/antagonistas & inibidores , Retina/metabolismo , Retina/patologia , Retina/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Linhagem CelularRESUMO
2D van der Waals (vdW) transition metal di-chalcogenides (TMDs) have garnered significant attention in the nonvolatile memory field for their tunable electrical properties, scalability, and potential for phase engineering. However, their complex switching mechanism and complicated fabrication methods pose challenges for mass production. Sputtering is a promising technique for large-area 2D vdW TMD fabrication, but the high melting point (typically Tm > 1000 °C) of TMDs requires elevated temperatures for good crystallinity. This study focuses on the low-Tm 2D vdW TM tetra-chalcogenides and identifies NbTe4 as a promising candidate with an ultra-low Tm of around 447 °C (onset temperature). As-grown NbTe4 forms an amorphous phase upon deposition that can be crystallized by annealing at temperatures above 272 °C. The simultaneous presence of a low Tm and a high crystallization temperature Tc can resolve important issues facing current phase-change memory compounds, such as high Reset energies and poor thermal stability of the amorphous phase. Therefore, NbTe4 holds great promise as a potential solution to these issues.
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The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has spread rapidly around the world. In order to prevent the spread of infection, city blockades and immigration restrictions have been introduced in each country, but these measures have a severe serious impact on the economy. This paper examines the possibility of both harvesting vibration energy and detecting mass by using a magnetostrictive alloy. Few efforts have been made to develop new magnetostrictive biosensor materials. Therefore, we propose magnetostrictive Fe-Co/Ni clad steel vibration energy harvesters with mass detection, and we numerically and experimentally discuss the effect of the proof mass weight on the frequency shift and output voltage induced by bending vibration. The results reveal that the frequency and output voltage decrease significantly as the mass increases, indicating that the energy harvesting device is capable of mass detection. In the future, device miniaturization and the possibility of virus detection will be considered.
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Undoubtedly, the coronavirus disease 2019 (COVID-19) has received the greatest concern with a global impact, and this situation will continue for a long period of time. Looking back in history, airborne transimission diseases have caused huge casualties several times. COVID-19 as a typical airborne disease caught our attention and reminded us of the importance of preventing such diseases. Therefore, this study focuses on finding a new way to guard against the spread of these diseases such as COVID-19. This paper studies the dynamic electromechanical response of metal-core piezoelectric fiber/epoxy matrix composites, designed as mass load sensors for virus detection, by numerical modelling. The dynamic electromechanical response is simulated by applying an alternating current (AC) electric field to make the composite vibrate. Furthermore, both concentrated and distributed loads are considered to assess the sensitivity of the biosensor during modelling of the combination of both biomarker and viruses. The design parameters of this sensor, such as the resonant frequency, the position and size of the biomarker, will be studied and optimized as the key values to determine the sensitivity of detection. The novelty of this work is to propose functional composites that can detect the viruses from changes of the output voltage instead of the resonant frequency change using piezoelectric sensor and piezoelectric actuator. The contribution of this detection method will significantly shorten the detection time as it avoids fast Fourier transform (FFT) or discrete Fourier transform (DFT). The outcome of this research offers a reliable numerical model to optimize the design of the proposed biosensor for virus detection, which will contribute to the production of high-performance piezoelectric biosensors in the future.
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Carbamazepine (CBZ) antibiotic organic contamination wastewater poses a huge threat to environmental safety. An advanced oxidation technology (Fe0/PDS/US) of using ultrasound (US) enhanced zero-valent iron/potassium persulfate (Fe0/PDS) can remove CBZ effectively. The optimal reaction conditions were determined by exploring the effect of single-factor experimental conditions such as ultrasonic power, ultrasonic frequency, CBZ concentration, solution pH, PDS dosage, and Fe0 dosage on the removal of CBZ. In addition, we also investigated into the effect of background ions (PO43-, HCO3-, Cl- and HA) on Fe0/PDS/US and analyzed the related results. The mechanism of CBZ removal in Fe0/PDS/US were explored by analyzing CBZ removal efficiency and reaction rates, the ion concentration of S2O82-, SO42-, Fe2+ and Fe3+, pH and the active radicals. The result indicates that US can improve the efficiency of activated PDS and expand the pH range of Fe0/PDS. It has prominent performance in catalytically degrading CBZ when the pH is 10.0. SO4â¢-, â¢OH and O2â¢- all coexist in the Fe0/PDS/US and make contribution to CBZ removal, whereas the SO4â¢- plays a key role. US can greatly promotes the degradation of target pollutant CBZ by speeding up the dissolution of the outer portion of iron powder, producing sufficient amount of Fe2+ with a continuous and stable way, and better activating S2O82- to generate sufficient SO4â¢- radicals. The degradation of CBZ may embrace three reaction processes, in which organic intermediate products with low molecular weight and biological toxicity is produced, boosting further mineralization and biodegradation of products. The Fe0/PDS/US is of great potential application value in removal of organic pollution and environmental purification.
Assuntos
Poluentes Químicos da Água , Biodegradação Ambiental , Carbamazepina , Ferro , Oxirredução , Poluentes Químicos da Água/análiseRESUMO
It is well known that the curing residual stress induced during a fabrication process has a great influence on the performance of piezoelectric composite devices. The purpose of this work was to evaluate the residual thermal stress of lead zirconate titanate piezoelectric fiber aluminum (Al) matrix (piezoelectric fiber/Al) composites generated during fabrication and to understand the effect of the residual thermal stress on the electromechanical response. The three-dimensional finite element method was employed, and the residual stress generated during the solidification process of the Al matrix was calculated. The output voltage was also calculated in the analysis when putting stresses on the composite materials in the length direction of the piezoelectric fiber. It was shown that the cooling from higher temperatures increases the electromechanical conversion capability. Furthermore, we also performed the simulation, and we recorded the output voltage under concentrated load to investigate its application as a load position detection sensor, and we also discussed the influence of the position by changing the modeling with a different fiber position in the Al. The residual stress of hot press molded piezoelectric fiber/Al composite was then measured, and the comparison was made with the calculated values. The simulation results revealed that our model predictions reproduced and explained the experimental observations of curing residual stress. After this study, similar models of composite materials can be analyzed by this simulation, and the result can be used to design piezoelectric composite materials.
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Cellulose nanofiber (CNF) has been accepted as a valid nanofiller that can improve the mechanical properties of composite materials by mechanical and chemical methods. The purpose of this work is to numerically and experimentally evaluate the mechanical behavior of CNF-reinforced polymer composites under tensile loading. Finite element analysis (FEA) was conducted using a model for the representative volume element of CNF/epoxy composites to determine the effective Young's modulus and the stress state within the composites. The possible random orientation of the CNFs was considered in the finite element model. Tensile tests were also conducted on the CNF/epoxy composites to identify the effect of CNFs on their tensile behavior. The numerical findings were then correlated with the test results. The present randomly oriented CNF/epoxy composite model provides a means for exploring the property interactions across different length scales.
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A highly site-selective N-heterocyclic carbene (NHC)-catalyzed benzoin-type cyclization of unsymmetrical dialdoses is developed to enable a divergent cyclitol synthesis. The choice of chiral NHCs and protecting groups affects the site-selectivity. The resulting inososes are converted into epi-, muco- and myo-inositols, and their chiral protected derivatives are formed in good yields.
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An N-heterocyclic carbene promotes cyclization of sulfonylalkynols and sulfonylalkynamides that accompanies 1,2-migration of the sulfonyl groups. This reaction provides a novel access to oxa- and azacycles possessing a pendent vinyl sulfone functionality, which, in turn, is amenable for further transformations.
Assuntos
Seio Carotídeo/fisiopatologia , Neoplasias Nasofaríngeas/complicações , Síncope/etiologia , Idoso , Carcinoma , Eletrocardiografia , Humanos , Masculino , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Síncope/diagnóstico , Síncope/fisiopatologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To assess left ventricular (LV) diastolic function in patients with dermatomyositis (DM) without clinically evident cardiovascular (CV) disease and to estimate whether there is an association between the duration of DM and LV diastolic dysfunction (LVDD). METHODS: The study included 51 patients with DM (43 women and 8 men) who had no clinically evident CV disease and 51 age-matched and sex-matched healthy controls. Echocardiographic and Doppler studies were conducted in all patients and controls. Early diastolic flow velocity/mitral annular early diastolic velocity (E/Em) was considered a marker for diastolic dysfunction. RESULTS: E/Em was elevated in 39 patients (76.5%) versus 27 controls (52.9%; p < 0.05). There were significant differences between patients versus control group in late diastolic flow velocity (A), E/A ratio, Em, Em/Am (mitral annular late diastolic velocity) ratio, E/Em ratio, and deceleration time (DT; p < 0.05). There was a weak correlation with disease duration between A (r = 0.373, p = 0.007), E/A ratio (r = -0.467, p = 0.001), Em (r = -0.474, p < 0.001), Em/Am ratio (r = -0.476, p < 0.001), E/Em ratio (r = 0.320, p = 0.022), and DT (r = 0.474, p < 0.001). Disease duration was associated with E/Em after controlling for age, sex, and other factors (p < 0.05). CONCLUSION: Our study confirms a high frequency of LVDD in DM patients without evident CV disease. The association between transmitral flow alteration and disease duration may suggest a subclinical myocardial involvement with disease progression.
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Velocidade do Fluxo Sanguíneo/fisiologia , Dermatomiosite/complicações , Disfunção Ventricular Esquerda/complicações , Adolescente , Adulto , Idoso , Dermatomiosite/diagnóstico por imagem , Dermatomiosite/fisiopatologia , Diástole , Progressão da Doença , Ecocardiografia Doppler , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Adulto JovemRESUMO
OBJECTIVE: To establish a community-based management model for heart failure patients under the professional guidance of upper first-class hospital staff. METHODS: Two hundreds heart failure (New York Heart Function II-IV) patients aged from 35 to 85 in two communities of Chengdu city were divided into two groups by cluster randomization: the management group and the control group. The community hospital doctors were trained for the evaluation and management of heart failure according standardized guidelines by upper first-class hospital doctors, and responsible for the management of patients in the management group. Meanwhile, the management group patients also received self-care education. Patients in control group were treated by community doctors without special training. Data including the community hospital doctors' knowledge rate of heart failure, positive diagnosis rate, and the rate for standardized medication for heart failure; the patients' knowledge rate of heart failure, the rate of drug compliance, the rate of standardized drug taken for heart failure, the rate of self-care in daily-life, the quality of life, the incidence of cardiovascular events, hospitalization time and cost were compared between the two groups. RESULTS: The community hospital doctors' knowledge rate of heart failure, the related knowledge for prevention and treatment on the causes of heart failure, the positive diagnosis rate, and the rate for standardized medication for heart failure [ß receptor blocker 77.3% (17/22); angiotensin-converting enzyme inhibitors 63.6% (14/22)] were significantly higher than doctors in the control group (all P < 0.05). There were 96 in the management group and 97 in the control group. Data were similar between the two groups at baseline. After (18.5 ± 0.5) months, the patient's knowledge rate of heart failure [100% (96/96) vs. 71.1% (69/97)], the rate of drug compliance [78.1% (75/96) vs. 13.4% (13/97)], the rate of standardized drug taken for heart failure[ß receptor blocker: 75.0% (72/96) vs. 8.2% (8/97); angiotensin-converting enzyme inhibitors: 60.4% (58/96)vs. 10.3% (10/97)], and the rate of self-care in daily-life [salt and food restriction:88.5% (85/96) vs. 29.9% (23/97); blood pressure monitoring: 83.3% (80/96) vs. 56.7% (55/97); weight monitoring:78.1% (75/96) vs. 13.4% (13/97)] were all significantly higher in the management group than in control group. For patients with New York Heart Function III-IV, the score of the LiHFe questionnaire (43.7 ± 9.2 vs. 49.5 ± 11.3), the incidence of cardiovascular events [63.3% (19/30) vs. 90.3% (28/31)], the days of hospitalization [(8.2 ± 3.2)days vs. (13.9 ± 10.9) days], and the cost for hospitalization [(2873.3 ± 401.6) Yuan vs. (4525.8 ± 6417.8) Yuan] were all significantly lower in the management group (n = 30) than in the control group (n = 31) (all P < 0.05). CONCLUSIONS: The community-based management model for heart failure patients in the community level is effective to improve the management and outcome in this cohort.