Low-density polyethylene (LDPE), as an excellent dielectric insulating material, is widely used in electrical equipment insulation, whereas its low thermal conductivity limits its further development ...and application. Hexagonal boron nitride (h-BN) filler was introduced into LDPE to tailor the properties of LDPE to make it more suitable for high-voltage direct current (HVDC) cable insulation application. We employed melt blending to prepare h-BN/LDPE thermally conductive composite insulation materials with different contents. We focused on investigating the micromorphology and structure, thermal properties, and electrical properties of h-BN/LDPE composites, and explained the space charge characteristics. The scanning electron microscope (SEM) results indicate that the h-BN filler has good dispersibility in the LDPE at a low loading (less than 3 phr (3 g of micron h-BN particles filled in 100g of LDPE)), as well as no heterogeneous phase formation. The results of thermal conductivity analysis show that the introduction of h-BN filler can significantly improve the thermal conductivity of composites. The thermal conductivity of the composite samples with 10 phr h-BN particles is as high as 0.51 W/(m·K), which is 57% higher than that of pure LDPE. The electrical performance illustrates that h-BN filler doping can significantly inhibit space charge injection and reduce space charge accumulation in LDPE. The interface effect between h-BN and the substrate reduces the carrier mobility, thereby suppressing the injection of charges of the same polarity and increasing the direct-current (DC) breakdown strength. h-BN/LDPE composite doped with 3 phr h-BN particles has excellent space charge suppression effect and high DC breakdown strength, which is 14.3% higher than that of pure LDPE.
The mechanism of receptor tyrosine kinase (RTK) over-activation due to mutations in their transmembrane (TM) domain is not well understood, and different mechansims have been proposed to contribute ...to pathogenesis. Here, we address the effect of two such pathogenic mutations (V664E in Neu and A391E in fibroblast growth factor receptor 3 (FGFR3)) on receptor activation in mammalian cells. We develop a quantitative description of receptor activation in terms of free energies of activation, and generate mathematical predictions of active fractions as a function of receptor expression. We test the mathematical predictions by comparing them to Western blot measurements of active fractions of Neu and chimeric Neu_FGFR3 receptors in CHO cells. We show that the predictions describe the experimental data, thus yielding a quantitative measure of receptor over-activation due to the two mutations studied. In CHO cells, the V664E mutation increases the Neu activation propensity by about –1.1 kcal/mol, while the increase due to the A391E mutation is about –0.7 kcal/mol. The two values are similar, and likely represent Glu-mediated stabilization of the active dimeric state. Thus, an increase of the order of ∼ –1 kcal/mol may be sufficient to transform normal signaling processes into pathogenic processes. The results of this study increase our knowledge of the mechanism behind RTK-mediated pathologies, and highlight the potential utility of inhibitors that target the dimerization process. They also suggest the cellular response to stimuli can be understood and predicted based on quantitative knowledge of interaction strengths between proteins involved in signaling.
This study aimed to optimize the detection conditions for surface-enhanced Raman spectroscopy (SERS) of single-stranded DNA (ssDNA) in four different buffers and explore the interaction between ...gonyautoxin (GTX1/4) and its aptamer, GO18. The influence of the silver colloid solution and MgSO
concentration (0.01 M) added under four different buffered conditions on DNA SERS detection was studied to determine the optimum detection conditions. We explored the interaction between GTX1/4 and GO18 under the same conditions as those in the systematic evolution of ligands by exponential enrichment technique, using Tris-HCl as the buffer. The characteristic peaks of GO18 and its G-quadruplex were detected in four different buffer solutions. The change in peak intensity at 1656 cm
confirmed that the binding site between GTX1/4 and GO18 was in the G-quadruplex plane. The relative intensity of the peak at 1656 cm
was selected for the GTX1/4-GO18 complex (I
/I
) to plot the ratio of GTX1/4 in the Tris-HCl buffer condition (including 30 μL of silver colloid solution and 2 μL of MgSO
), and a linear relationship was obtained as follows: Y = 0.1867X + 1.2205 (R
= 0.9239). This study provides a basis for subsequent application of SERS in the detection of ssDNA, as well as the binding of small toxins and aptamers.
Stem cells have emerged as a potential therapy for a range of neural insults, but their application in Alzheimer's disease (AD) is still limited and the mechanisms underlying the cognitive benefits ...of stem cells remain to be elucidated. Here, the effects of clinical‐grade human umbilical cord‐derived mesenchymal stem cells (hUC‐MSCs) on the recovery of cognitive ability in SAMP8 mice, a senescence‐accelerated mouse model of AD is explored. A functional assay identifies that the core functional factor hepatocyte growth factor (HGF) secreted from hUC‐MSCs plays critical roles in hUC‐MSC‐modulated recovery of damaged neural cells by down‐regulating hyperphosphorylated tau, reversing spine loss, and promoting synaptic plasticity in an AD cell model. Mechanistically, structural and functional recovery, as well as cognitive enhancements elicited by exposure to hUC‐MSCs, are at least partially mediated by HGF in the AD hippocampus through the activation of the cMet‐AKT‐GSK3β signaling pathway. Taken together, these data strongly implicate HGF in mediating hUC‐MSC‐induced improvements in functional recovery in AD models.
This study explores the effects of clinical‐grade hUC‐MSCs on the recovery of cognitive ability of Alzheimer's disease (AD). All results uncover that HGF secreted from hUC‐MSCs, mediates the beneficial effects of hUC‐MSCs on functional recovery of damaged neural cells by downregulating hyperphosphorylated tau, improving neurofibrillary tangles, reversing spine loss, and promoting synaptic plasticity in AD hippocampus through the cMet‐AKT‐GSK3β signaling pathway.
Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received ...first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (
) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for
colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had
mutation and
-type colon cancer, and his PD-1
CD8
and CD3
CD19
CD14
CD16
HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated,
-type and
-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials.
Low-density polyethylene (LDPE) has excellent dielectric properties and is extensively used in electrical equipment. Hexagonal boron nitride (h-BN) is similar to a graphite-layered structure, and ...alumina fiber (Al2O3) has high-temperature resistance and a strong performance. Herein, we prepared Al2O3-h-BN/LDPE nanocomposites by using LDPE as the matrix material and h-BN and Al2O3 as the fillers. The influence of different doping contents and the mass ratio of Al2O3 and h-BN (1:1) to LDPE on the electrical properties and thermal conductivity of the nanocomposites was examined. The results showed that the suppression effect on space charge was the most obvious and average. The charge density was the lowest and had the minimum decay rate when the doping content was 2%. The breakdown strength of the film reached the maximum value of 340.1 kV/mm, which was 12.3% higher than that of the pure LDPE (302.8 kV/mm). The thermal diffusivity of the composite sample was also higher than that of the single h-BN-doped sample when the content of h-BN and Al2O3 was 7%. The thermal conductivity was 59.3% higher than that of the pure LDPE sample and 20% higher than that of h-BN/LDPE.
The Chinese Continental Scientific Drilling (CCSD) Project offers a unique opportunity for studying the thermal regime of the Dabie‐Sulu ultrahigh‐pressure metamorphic belt. In this paper, we report ...measurements of borehole temperature, thermal conductivity, and radiogenic heat production from the 5158 m deep main hole (CCSD MH). We have obtained six continuous temperature profiles from this borehole so far. The temperature logs show a transient mean thermal gradient that has increased from 24.38 to 25.28 K km−1 over a period of about 1.5 years. We measured thermal conductivities and radiogenic heat productions on more than 400 core samples from CCSD MH. The measured thermal conductivities range between 1.71 and 3.60 W m−1 K−1, and the radiogenic heat productions vary from 0.01 μW m−3 to over 5.0 μW m−3, with a mean value of 1.23 ± 0.82 μW m−3 for the upper 5‐km layer of the crust. The heat productions in CCSD MH appear to be more rock‐type than depth‐dependent and, over the depth range of CCSD MH, do not fit the popular model of heat production decreasing exponentially with increasing depth. The measured heat flow decreases with depth from ∼75 mW m−2 near the surface to ∼66 mW m−2 at a depth of 4600 m. High heat flow anomalies occur at ∼1000 and ∼2300 m, and low anomalies occur at 3300–4000 m. A preliminary two‐dimensional numerical model suggests that both radiogenic heat production and thermal refraction due to structural heterogeneity are at least partially responsible for the vertical variation of heat flow in CCSD MH.
The Pearl River Mouth Basin (PRMB) and Qiongdongnan Basin (QDNB) are oil and gas bearing basins in the northern margin of the South China Sea (SCS). Geothermal survey is an important tool in ...petroleum exploration. A large data set comprised of 199 thermal conductivities, 40 radioactive heat productions, 543 measured geothermal gradient values, and 224 heat flow values has been obtained from the two basins. However, the measured geothermal gradient data originated from diverse depth range make spatial comparison a challenging task. Taking into account the variation of conductivity and heat production of rocks, we use a “uniform geothermal gradient” to characterize the geothermal gradient distribution of the PRMB and QDNB. Results show that, in the depth interval of 0–5
km, the “uniform geothermal gradient” in the PRMB varies from 17.8
°C/km to 50.2
°C/km, with an average of 32.1
±
6.0
°C/km. In comparison, the QDNB has an average “uniform geothermal gradient” of 31.9
±
5.6
°C/km and a range between 19.7
°C/km and 39.5
°C/km. Heat flows in the PRMB and QDNB are 71.3
±
13.5
mW/m
2 and 72.9
±
14.2
mW/m
2, respectively. The heat flow and geothermal gradient of the PRMB and QDNB tend to increase from the continental shelf to continental slope owing to the lithosphereic/crustal thinning in the Cenozoic.
Chloranthus serratus (Thunb.) Roem. et Schult. (Chloranthaceae) is an herb widely used as a folk medicine treating inflammatory diseases, although it is toxic.
To investigate hepatotoxicity and ...related mechanisms induced by ethanol extracts of different parts of C. serratus in rats.
Sprague Dawley rats were divided into control (Con), ethanol extract of roots (ER), stems (ES), and leaves (EL) groups, and acute oral toxicity studies were conducted. The rats received doses of 4.14, 3.20, and 1.16 g/kg/d extracts for 14 days, respectively. Liver index, liver function and oxidative stress biomarkers, liver pathology, ultrastructure, TNF-α, ICAM-1, and Nrf2/HO-1 proteins expression levels were determined.
The LD
50
of ER, ES, and EL were higher than 10.35, 8.05, and 2.90 g/kg/p.o., respectively. The liver indexes in the extract groups increased significantly. EL dramatically increased TP, GLB, AST, ALT, ALP, TBA, MDA, ICAM-1, and TNF-α levels (p < 0.01), and induced the most obvious pathological and ultrastructural changes. ES and EL obviously decreased the T-SOD, GSH, CAT, and CHOL levels. Nrf2 and HO-1 proteins expression was reduced significantly in ES (0.77 ± 0.06, 2.33 ± 0.20) and EL (0.23 ± 0.04, 2.14 ± 0.16) groups, and reduced slightly in ER (1.08 ± 0.10; 3.39 ± 0.21) group.
ES and EL induce stronger hepatotoxicity than ER through oxidative stress and the Nrf2/HO-1 pathway, and the root is a better medicinal part, which provides a basis for clinical research, safe applications, and reasonable development of C. serratus.
Abstract Background ATPase activity and the antioxidant function of intestinal tissue can reflect intestinal cell metabolic activity and oxidative damage, which might be related to intestinal ...function. However, the specific influence of intestinal ATPase activity and antioxidant function on growth performance, feed conversion efficiency, and the intestinal microbiota in sheep remains unclear. Results This study analyzed the correlation between ATPase activity and antioxidant function in the jejunum of 92 Hu sheep and their growth performance and feed conversion efficiency. Additionally, individuals with the highest (H group) and lowest (L group) jejunum MDA content and Na + K + -ATPase activity were further screened, and the effects of jejunum ATPase activity and MDA content on the morphology and microbial community of sheep intestines were analyzed. There was a significant correlation between jejunum ATPase and SOD activity and the initial weight of Hu sheep ( P < 0.01). The H-MDA group exhibited significantly higher average daily gain (ADG) from 0 to 80 days old and higher body weight (BW) after 80 days. ATPase and SOD activities, and MDA levels correlated significantly and positively with heart weight. The jejunum crypt depth and circular muscle thickness in the H-ATP group were significantly higher than in the L-ATP group, and the villus length, crypt depth, and longitudinal muscle thickness in the H-MDA group were significantly higher than in the L-MDA group ( P < 0.01). High ATPase activity and MDA content significantly reduced the jejunum microbial diversity, as indicated by the Chao1 index and observed species, and affected the relative abundance of specific taxa. Among species, the relative abundance of Olsenella umbonata was significantly higher in the H-MDA group than in the L-MDA group ( P < 0.05), while Methanobrevibacter ruminantium abundance was significantly lower than in the L-MDA group ( P < 0.05). In vitro culture experiments confirmed that MDA promoted the proliferation of Olsenella umbonata . Thus, ATPase and SOD activities in the jejunum tissues of Hu sheep are predominantly influenced by congenital factors, and lambs with higher birth weights exhibit lower Na + K + -ATPase, Ca 2+ Mg 2+ -ATPase, and SOD activities. Conclusions The ATPase activity and antioxidant performance of intestinal tissue are closely related to growth performance, heart development, and intestinal tissue morphology. High ATPase activity and MDA content reduced the microbial diversity of intestinal tissue and affect the relative abundance of specific taxa, representing a potential interaction between the host and its intestinal microbiota.
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