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Radioiodine (131I) is one of the most well-known and widely used targeted therapies. In thyroid carcinoma (THCA), it has been applied for more than eight decades and is still being utilized to eliminate remnants after resection and to reduce tumor metastases. Here, we aimed to investigate if lysine methyltransferase 2B (KMT2B) silencing could confer 131I resistance to THCA cells and the epigenetic mechanism behind. RT-qPCR, immunohistochemistry and western blot revealed that KMT2B was poorly expressed in THCA cells, and 131I resistance of cells led to a further decrease in KMT2B expression. EdU, colony formation, TUNEL, and tumor growth and metastasis assays showed that overexpression of KMT2B sensitized THCA cell to 131I and inhibited cell growth and metastasis. Further bioinformatics prediction and functional assay validation revealed that KMT2B elevated SHPRH expression via H3K4me3 modification in the SHPRH promoter, and that SHPRH modulated FYN ubiquitination, thereby promoting its protein degradation. We finally proved that the 131I-resistant cells regained resistance to 131I by FYN overexpression in the presence of KMT2B overexpression in vitro and in vivo. Therefore, we conclude that the overexpression of KMT2B represents a potential target for THCA therapy.Vitamin D3 is associated with improvements in insulin resistance and glycemia. In this study, we investigated the short-term effect of 1α,25(OH)2 Vitamin D3 (1,25-D3) and cholecalciferol (vitamin D3) on the glycemia and insulin sensitivity of control and dexamethasone-induced insulin-resistance rats. 45Ca2+ influx responses to 1,25-D3 and its role in insulin secretion were investigated in isolated pancreatic islets from control rats. In vivo, 5 days treatment with 1,25-D3 (i.p.) prevented insulin resistance in dexamethasone-treated rats. Treatment with 1,25-D3 improved the activities of hepatic enzymes, serum lipids and calcium concentrations in insulin-resistant rats. 25-D3 (o.g.) does not affect insulin resistance. In pancreatic islets, 1,25-D3 increased insulin secretion and stimulated rapid response 45Ca2+ influx. The stimulatory effect of 1,25-D3 on 45Ca2+ influx was decreased by diazoxide, apamine, thapsigargin, dantrolene, 2-APB, nifedipine, TEA, PKA, PKC, and cytoskeleton inhibitor, while it was increased by glibenclamide and N-ethylmaleimide. The stimulatory effect of 1,25-D3 on 45Ca2+ influx involves the activation of L-type VDCC, K+-ATP, K+-Ca2+, and Kv channels, which augment cytosolic calcium. These ionic changes mobilize calcium from stores and downstream activation of PKC, PKA tethering vesicle traffic and fusion at the plasma membrane for insulin secretion. This is the first study highlighting the unprecedented role of 1,25-D3 (short-term effect) in the regulation of glucose homeostasis and on prevention of insulin resistance. Furthermore, this study shows the intracellular β-cell signal transduction of 1,25-D3 through the modulation of pivotal ionic channels and proteins exhibiting a coordinated exocytosis of vesicles for insulin secretion.While cryo-electron microscopy (cryo-EM) has revolutionized the structure determination of supramolecular protein complexes that are refractory to structure determination by X-ray crystallography, structure determination by cryo-EM can nonetheless be complicated by excessive conformational flexibility or structural heterogeneity resulting from weak or transient protein-protein association. Since such transient complexes are often critical for function, specialized approaches must be employed for the determination of meaningful structure-function relationships. Here, we outline examples in which transient protein-protein interactions have been visualized successfully by cryo-EM in the biosynthesis of fatty acids, polyketides, and terpenes. These studies demonstrate the utility of chemical crosslinking to stabilize transient protein-protein complexes for cryo-EM structural analysis, as well as the use of partial signal subtraction and localized reconstruction to extract useful structural information out of cryo-EM data collected from inherently dynamic systems. While these approaches do not always yield atomic resolution insights on protein-protein interactions, they nonetheless enable direct experimental observation of complexes in assembly-line biosynthesis that would otherwise be too fleeting for structural analysis.Shale gas, an emerging oil-bearing and pillar industry at home and abroad, has a very large impact on economic development and industry, but the resulting emerging pollutants pose a serious threat to the environment. Drilling cuttings, the primary byproduct of the exploration and mining of shale gas, are potentially hazardous types of waste that seriously deplete land resources and pose environmental safety problems. In this paper, a long-term static volatilization experiment was conducted to study the volatilization of polycyclic aromatic hydrocarbons (PAHs) in the oil-based residue of shale gas drill cuttings. selleck products Furthermore, the effects of some relevant environmental factors controlling the volatilization behavior were evaluated, including different particle sizes, temperatures and illuminances. The results showed that (1) the volatilization concentrations of PAHs gradually increased with prolonged volatilization time. PAHs with smaller ring numbers were present at the highest concentrations among the detected PAHs, and they were more readily volatilized and could be detected earlier. (2) The C-history method was found to significantly describe the kinetic process of the volatilization of PAHs. (3) Different environmental factors had different effects on the volatilization of PAHs. We found that increasing the temperature and illuminance and decreasing the particle size increased volatility. Through canonical correspondence analysis, PAHs volatilization was found to be a complex process, so volatilization tests under simulated environmental conditions are of scientific and environmental interest.Fe-Ce-based composite catalysts were prepared and used for As2O3 catalytic oxidation and adsorption. They were characterized by XRD, BET, H2-TPR, Raman, SEM and XPS. The results suggests Fe, La and Zr can be partially doped into CeO2 lattice to form solid solutions. Compared with pure Fe2O3, the composite catalysts have stronger low-temperature reducibility, especially La3+ doping is beneficial to the formation of more low-temperature active sites. Raman and XPS measurements disclose the presence of oxygen vacancy and surface adsorbed oxygen in composite catalysts and these are more prominent in FeCeLaO. Ce3+ ratio increases to 18.30% after reaction, which confirms part of Ce4+ can participate in As2O3 oxidation and be reduced to Ce3+. The oxidation and adsorption capacity for As2O3 were investigated at different temperatures and O2 concentrations. The results show FeCeLaO exhibits excellent activity at middle-low-temperatures of 200-400 °C, the oxidation efficiency of As2O3 can reach 100%, the total adsorbed arsenic at 400 °C reaches 583.7 μg/g, which is 1.8 times of pure Fe2O3 at 600 °C. As2O3 oxidation mechanism over FeCeLaO with/without O2 was proposed through the Mars-Maessen theory with the aid of surface-active oxygen. The abundant oxygen vacancy defects and active chemisorbed oxygen play important roles and guarantee an efficient As2O3 oxidation, which is also the essential reason why the composite catalysts can effectively oxidize and adsorb As2O3 at middle-low-temperature of 200-400 °C, while pure Fe2O3 can only be at high temperature of 600-700 °C.Per- and polyfluoroalkyl substances (PFAS) have received continuous attention; however, there is limited understanding of their sources in the atmosphere and related human exposure risks. This study measured PFAS in the atmospheric total suspended particles collected from Karachi, Pakistan, during the winter. Among the quantified PFAS, perfluorobutanoic acid (PFBA) showed the highest average concentration (3.11 ± 2.64 pg/m3), accounting for 32% of the total PFAS. Wind speed was positively correlated with perfluorohexanoic acid (PFHxA) and N-ethyl perfluorooctanesulfonamide (N-EtFOSA), while relative humidity was negatively correlated with perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Weighted potential source contribution function (WPSCF) and concentration weighted trajectory (WCWT) analyses suggested that northwestern Pakistan and western Afghanistan areas were highly associated with the long-range atmospheric transport of PFAS. We also calculated the daily intake of PFAS via inhalation, which were in the range of 0.07-3.98 and 0.01-0.33 pg/kg bw/d for children and adults, respectively. The calculated hazard quotient (HQ) of PFOS and PFOA was significantly lower than 1, indicating less or unlikely to cause non-carcinogenic effect via inhalation exposure. Overall, this study contributes to the understanding of geographic origins and human inhalation risks of airborne PFAS on a regional scale.Herein, the major biochar properties were correlated with electron transfer of zerovalent iron (ZVI) and contribution of biomass constituents to biochar property was ascertained to optimize electron transfer of ZVI. To this end, five respective stalk-type and wood-type lignocellulosic biomasses were pyrolzed at 600 °C to prepare biochars to harbor ZVI (ZVI/BC). Thermogravimetric analysis demonstrated woody biomasses decomposed more intensively at higher temperature relative to stalky biomass. ZVI/BC were characterized with Raman, X-ray diffraction, and electrochemical analyses including electron donating capacity (EDC) and electron accepting capacity (EAC). Pearson correlation and partial least-squares (PLS) analyses confirmed that Cr(VI) reduction capacity was negatively related to Tafel corrosion potential and intensity ratio of ID/IG, but significantly positively-related to EDC of BC, in which EDC was a predominant attribute to contribute to reductive capacity toward Cr(VI) reduction. That is, greater EDC and higher graphitic carbon structure of biochar due to cellulose and hemicellulose components favor electron transfer of ZVI toward Cr(VI) reduction.Characterization of the country internal variability of arsenic (As) accumulation in rice grain across different rice production regions is very important in order to analyze its compliance with international and regional limits. A robust sampling study scheme (n = 150 samples) was performed to determine total arsenic (tAs) and inorganic (iAs) levels from polished rice grain covering all rice producing regions along two growing seasons. The mean and median concentration of tAs were 0.178 mg kg-1 and 0.147 mg kg-1, with a minimum and maximum value of 0.015 mg kg-1 and 0.629 mg kg-1, respectively and a coefficient of variation of 63.6%. The mean and median concentration of iAs were 0.062 mg kg-1 and 0.055 mg kg-1 respectively ranging from 0.005 mg kg-1 up to a maximum of 0.195 mg kg-1 and a coefficient of variation of 51.5%. A moderate correlation was revealed within iAs and tAs. Levels of iAs in all of the samples were below the international limits of 0.2 mg kg-1 according to the international limits for human health by the Codex Alimentarius (FAO and WHO, 2019).
Read More: https://www.selleckchem.com/products/17-AAG(Geldanamycin).html
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