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•P-F-HKUST-1 synergistically increases HIF-1α production and stability, finally restores ischemic hindlimb blood flow rapidly.
Critical limb ischemia (CLI) remains a significant ...clinical challenge with high morbidity and mortality. Considering the critical role of hypoxia-inducible factor 1α (HIF-1α) in hypoxic site to induce angiogenesis by regulating the expression of growth factors, we prepared a cooperative composite (P-F-HKUST-1) by mixing thermo-responsive hydrogel (PPCN) with folic acid modified copper-based MOFs (F-HKUST-1) for the hindlimb ischemia therapy. The gelation of P-F-HKUST-1 in hindlimb muscle generated a more serious ischemia environment and subsequently induced the expression of HIF-1α, while the slowly released Cu2+ from P-F-HKUST-1 increased HIF-1α stability by inactivating the factor-inhibiting hypoxia-inducible factor 1 (FIH-1), which synergistically induced the productions of downstream growth factors and finally restored the blood perfusion rapidly. In addition, P-F-HKUST-1 hydrogel exhibited a long in vivo retention time, which endowed the sustaining action on HIF-1α to reduce the frequency of administration. The rapid blood flow recovery, together with the good biocompatibility suggested that P-F-HKUST-1 could be a potential novel combined therapy (HIF-1α stimulation and stabilization) for critical limb ischemia.
Bupivacaine (BP) is a commonly clinically used local anesthetic (LA). Current studies suggest that neurological complications are increased in diabetic patients after LA application, but the ...molecular mechanism is poorly understood. LA-induced autophagy and neuronal injury have been reported. We hypothesized that a high-glucose environment aggravates BP-induced autophagic damage. Mouse dorsal root ganglion (DRG) neurons were treated with BP in a high-glucose environment, and the results showed that reactive oxygen species (ROS) levels increased, autophagy was activated, autophagy flux was blocked, and cell viability decreased. Pretreatment with the ROS scavenger N-acetyl-cysteine (NAC) attenuated ROS-mediated autophagy regulation. Moreover, the expression of the long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) increased, and NAC and TUG1 siRNA inhibited the expression of TUG1/mammalian target of rapamycin (mTOR) in DRGs treated with BP in a high-glucose environment. Intriguingly, contrary to previous reports on a positive effect on neurons, we found that rapamycin, an autophagy activator, and chloroquine, an autophagy and lysosome inhibitor, both exacerbated autophagic damage. These data suggest that a high-glucose environment exacerbated BP induced ROS-dependent autophagic damage in DRG neurons through the TUG1/mTOR signaling pathway, which provides a theoretical basis and target for the clinical prevention and treatment of BP neurotoxicity in diabeties.
The research aimed to explore the biological role of p53 protein and long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in bupivacaine (bup)-induced neurotoxicity. Our work treated dorsal ...root ganglion (DRG) cells with bup, detected cell viability through CCK-8, apoptosis through TUNEL assays, DeoxyriboNucleic Acid (DNA) damage through γ-H2AX protein and comet assay, including p53 mRNA, protein and TUG1 expression through q-PCR and western blot, furthermore, cell viability and DNA damage were determined after the silencing of p53 and TUG1, biological information and TUG1 FISH combined with p53 protein immunofluorescence (IF) was performed to determine the cellular localization of these molecule. In vivo experiments, we explored the impact of intrathecal injection of bup on p53 mRNA and protein, TUG1, γ-H2AX protein expression. The results showed that bup was available to signally decreased cell viability, promoted apoptosis rate and DNA damage, additionally, bup increased p53 mRNA and protein and TUG1 expression. P53 siRNA and TUG1 siRNA significantly increased DNA damage. Furthermore, bioinformatics analysis and colocalization experiments revealed that the p53 protein is a transcription factor of TUG1, in vivo experiment, intrathecal injection of bup increased the p53 mRNA, p53 protein, TUG1 and γ-H2AX protein in the murine DRG. In this study, it was found p53 and TUG1 promote the repair of the DNA damage induced by bup in murine dorsal root ganglion cells, suggesting a new strategy for the amelioration of bup-induced neurotoxicity.
•High glucose causes an increase in cell toxicity induced by BP.•High glucose aggravated BP-induced DNA damage and apoptosis.•High glucose aggravated BP-induced DNA damage through inhibit DNA-PK/Ku70 ...protein.
Bupivacaine (BP) is commonly used as a local anaesthetic(LA) in the clinic, but it can also cause neurotoxicity, especially in patients with diabetes. Previous studies have found that high-glucose environments can aggravate BP-induced DNA damage in nerve cells. Ku70 is subunit of the DNA damage repair enzyme DNA-PK. This study was designed to determine whether high-glucose conditions enhance BP neurotoxicity and DNA damage by inhibiting Ku70 expression.
We examined the effect of BP on apoptosis and DNA damage in murine dorsal root ganglion (DRG) neurons under hyperglycaemic conditions. Untreated DRG cells and DRG cells pretreated with NU7441, a DNA-PK inhibitor, were cultured for 3 days under normal culture conditions or with 50 mM glucose, and the cells were then treated with BP for 3 h. DNA damage was investigated via comet assays, the ratio of early to late apoptotic cells was assessed by Annexin V-FITC/PI staining, and cell viability was measured by CCK-8 assays. The protein expression levels of DNA-PK, Ku70, Bax, Bcl-2 and γH2ax were measured by immunofluorescence or Western blotting.
Compared to its effect under normal culture conditions, BP treatment led to decreased cell viability and increased DNA damage in DRG cells grown under high-glucose conditions. The rate of DRG cell apoptosis and the expression of γH2ax, the ratio of Bax to Bcl-2 also increased under the high-glucose conditions. Furthermore, Ku70 expression was inhibited. The DNA-PK inhibitor, NU7441, could significantly inhibit DNA-PK and Ku70 expression, simultaneously further aggravating BP-induced apoptosis and DNA damage under high-glucose conditions.
These data indicate that hyperglycaemia may enhance BP-induced neurotoxicity and DNA damage by inhibiting the DNA repair protein Ku70.
Tin oxide(SnO2) hollow microspheres with narrow size distribution were prepared by a facile one-pot microwave-assisted spray pyrolysis method. The effect of temperature on microstructural and optical ...properties was investigated by X-ray diffraction(XRD), scanning electron microscope(SEM), high resolution transmission electron microscope(HRTEM), and UV-Vis spectrophotometer(UV-Vis), respectively.The SnO2 particles obtained at and above 700?C are tetragonal rutile structure with high purity and smooth surface morphology, which consist of well-interconnected SnO2 nanocrystallines and the shell thickness was about 26 nm. UV-Vis absorption values were quite low in visible light region and high in ultraviolet region, indicating the possible utilization for optical purpose of the as-prepared SnO2. The band gaps were 3.88 and 4.07 e V for SnO2 synthesized at 700 and 800?C, respectively. As compared to traditional electrical heating or flame modes, microwave heating introduced here demonstrates a highefficiency, environmentally benign, and time-and energy-saving technology to synthesize advanced powders.
The Triassic-Jurassic (Tr-J) boundary marks a major extinction event, which (~200 Ma)resulted in global extinctions of fauna and flora both in the marine and terrestrial realms. There prevail great ...challenges in determining the exact location of the terrestrial Tr-J boundary, because of endemism of taxa and the scarcity of fossils in terrestrial settings leading to difficulties in linking marine and terrestrial sedimentary successions. Investigation based on palynology and bivalves has been carried out over a 1113 m thick section, which is subdivided into 132 beds, along the Haojiagou valley on the southern margin of the Junggar Basin of the northern Xinjiang, northwestern China. The terrestrial Lower Jurassic is conformably resting on the Upper Triassic strata. The Upper Triassic covers the Huangshanjie Formation overlaid by the Haojiagou Formation, while the Lower Jurassic comprises the Badaowan Formation followed by the Sangonghe Formation. Fifty six pollen and spore taxa and one algal taxon were identified from the sediments. Based on the key-species and abundance of spores and pollen, three zones were erected: the Late Triassic (Rhaetian) Aratrisporites-Alisporites Assemblage, the Early Jurassic (Hettangian) Perinopollenites-Pinuspollenites Assemblage, and the Sinemurian Perinopollenites-Cycadopites Assemblage. The Tr-J boundary is placed between bed 44and 45 coincident with the boundary between the Haojiagou and Badaowan formations. Beds with Ferganoconcha (?), Unio-Ferganoconcha and Waagenoperna-Yananoconcha bivalve assemblages are recognized. The Ferganoconcha (?) bed is limited to the upper Haojiagou Formation,Unio- Ferganoconcha and Waagenoperna- Yananoconcha assemblages are present in the middle and upper members of the Badaowan Formation. The sedimentary succession is interpreted as terrestrial with two mainly lake deposit intervals within Haojiagou and Badaowan formations, yielding fresh water algae and bivalves. However, the presence of brackish water algae Tasmanites and the marine-littoral facies bivalve Waagenoperna from the Badaowan Formation indicate that the Junggar Basin was influenced by sea water caused by transgressions from the northern Tethys, during the Sinemurian.
The present work explores the application of microwave heating for the melting of powdered tin. The mor- phology and particle size of powdered tin prepared by the centrifugal atomization method were ...charac- terized. The tin particles were uniform and spherical in shape, with 90% of the particles in the size range of 38-75μm. The microwave absorption characteristic of the tin powder was assessed by an estimation of the dielectric properties. Microwave penetration was found to have good volumetric heating on powdered tin. Conduction losses were the main loss mechanisms for powdered tin by microwave heating at temperatures above 150 ℃. A 20 kW commercial-scale microwave tin-melting unit was designed, developed, and utilized for production. This unit achieved a heating rate that was at least 10 times higher than those of conventional methods, as well as a far shorter melting duration. The results suggest that microwave heating accelerates the heating rate and shortens the melting time. Tin recovery rate was 97.79%, with a slag ratio of only 1.65% and other losses accounting for less than 0.56%. The unit energy consumption was only 0.17 (kW·h)·kg-1- far lower than the energy required by conventional melting methods. Thus, the microwave melting process improved heating efficiency and reduced energy consumption.
Abstract
The remarkable advantages of heterointerface and defect engineering and their unique electromagnetic characteristics inject infinite vitality into the design of advanced carbon-matrix ...electromagnetic wave absorbers. However, understanding the interface and dipole effects based on microscopic and macroscopic perspectives, rather than semi-empirical rules, can facilitate the design of heterointerfaces and defects to adjust the impedance matching and electromagnetic wave absorption of the material, which is currently lacking. Herein, CuCo
2
S
4
@Expanded Graphite heterostructure with multiple heterointerfaces and cation defects are reported, and the morphology, interfaces and defects of component are regulated by varying the concentration of metal ions. The results show that the 3D flower-honeycomb morphology, the crystal-crystal/amorphous heterointerfaces and the abundant cation defects can effectively adjust the conductive and polarization losses, achieve the impedance matching balance of carbon materials, and improve the absorption of electromagnetic wave. For the sample CEG-6, the effective absorption of Ku band with RL
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of −72.28 dB and effective absorption bandwidth of 4.14 GHz is realized at 1.4 mm, while the filler loading is only 7.0 wt. %. This article reports on the establishment of potential relationship between crystal-crystal/amorphous heterointerfaces, cation defects, and the impedance matching of carbon materials.
•A wind speed forecasting and wind energy simulation management system developed.•A robust novel hybrid system based on three modular is proposed.•A multi-objective optimization algorithm is ...developed to optimize the parameters.•The model selection module searches the optimal forecasting values.•The conversion of wind power to electric energy had been discussed.
Wind energy is of increasing interest to wind farm administrators as a clean and renewable energy source. Accurate wind speed forecasting and effective wind energy simulation can increase the capability of wind power combined with a grid and decrease the operating cost of wind farms. However, many previous studies have been restricted to wind speed forecasting, ignoring wind energy simulations. Thus, grid management cannot effectively estimate the power production of wind farms and leads to an increase in the abandonment wind rate in wind farms. In this study, a wind farm auxiliary management system is developed, which includes two modules: wind speed forecasting and wind energy simulation. In the wind speed forecasting module, first, a data mining algorithm is used to analyze different features of wind speed time series data in a wind farm. Subsequently, a feature selection algorithm is used to determine the representative wind speed time series of the wind farm, and it is combined with a data preprocessing method to effectively eliminate the noise of the original wind speed time series. Second, six hybrid neural network forecasting models based on a modified multi-objective algorithm are established to forecast wind speed. Finally, they are combined with a model selection strategy to yield the best forecasting value for each time point. In the wind energy simulation module, using Betz's theory, the physical transformation process of a wind turbine is estimated to determine the range of wind power generation.