Targeting mutant p53 stabilization for cancer therapy.

Over 50% cancer bears TP53 mutation, the highly stabilized mutant p53 protein drives the tumorigenesis and progression. Mutation of p53 not only cause loss-of-function and dominant-negative effects (DNE), but also results in the abnormal stability by the regulation of the ubiquitin-proteasome system and molecular chaperones that promote tumorigenesis through gain-of-function effects. The accumulation of mutant p53 is mainly regulated by molecular chaperones, including Hsp40, Hsp70, Hsp90 and other biomolecules such as TRIM21, BAG2 and Stat3. In addition, mutant p53 forms prion-like aggregates or complexes with other protein molecules and result in the accumulation of mutant p53 in tumor cells. Depleting mutant p53 has become one of the strategies to target mutant p53. This review will focus on the mechanism of mutant p53 stabilization and discuss how the strategies to manipulate these interconnected processes for cancer therapy.

Synthesis and Evaluation of LaBaCo2-xMoxO5+δ Cathode for Intermediate-Temperature Solid Oxide Fuel Cells.

LaBaCo2-xMoxO5+δ (LBCMx, x = 0-0.08) cathodes synthesized by a sol-gel method were evaluated for intermediate-temperature solid oxide fuel cells. The limit of the solid solubility of Mo in LBCMx was lower than 0.08. As the content of Mo increased gradually from 0 to 0.06, the thermal expansion coefficient decreased from 20.87 × 10-6 K-1 to 18.47 × 10-6 K-1. The introduction of Mo could increase the conductivity of LBCMx, which varied from 464 S cm-1 to 621 S cm-1 at 800 °C. The polarization resistance of the optimal cathode LBCM0.04 in air at 800 °C was 0.036 Ω cm2, reduced by a factor of 1.67 when compared with the undoped Mo cathode. The corresponding maximum power density of a single cell based on a YSZ electrolyte improved from 165 mW cm-2 to 248 mW cm-2 at 800 °C.

Increasing sulfate concentration and sedimentary decaying cyanobacteria co-affect organic carbon mineralization in eutrophic lake sediments.

Sulfate (SO42-) concentrations in eutrophic lakes are continuously increasing; however, the effect of increasing SO42- concentrations on organic carbon mineralization, especially the greenhouse gas emissions of sediments, remains unclear. Here, we constructed a series of microcosms with initial SO42- concentrations of 0, 30, 60, 90, 120, 150, and 180 mg/L to study the effects of increased SO42- concentrations, coupled with cyanobacterial blooms, on organic carbon mineralization in Lake Taihu. Cyanobacterial blooms promoted sulfate reduction and released a large amount of inorganic carbon. The SO42- concentrations in cyanobacteria treatments significantly decreased and eventually reached close to 0. As the initial SO42- concentration increased, the sulfate reduction rates significantly increased, with maximum values of 9.39, 9.44, 28.02, 30.89, 39.68, and 54.28 mg/L∙d for 30, 60, 90, 120, 150, and 180 mg/L SO42-, respectively. The total organic carbon content in sediments (51.16-52.70 g/kg) decreased with the initial SO42- concentration (R2 = 0.97), and the total inorganic carbon content in overlying water (159.97-182.73 mg/L) showed the opposite pattern (R2 = 0.91). The initial SO42- concentration was positively correlated with carbon dioxide (CO2) emissions (R2 = 0.68) and negatively correlated with methane (CH4) emissions (R2 = 0.96). The highest CO2 concentration and lowest CH4 concentration in the 180 mg/L SO42- treatment were 1688.78 and 1903 µmol/L, respectively. These biogeochemical processes were related to competition for organic carbon sources between sulfate reduction bacteria (SRB) and methane production archaea (MPA) in sediments. The abundance of SRB was positively correlated with the initial SO42- concentration and ranged from 6.65 × 107 to 2.98 × 108 copies/g; the abundance of MPA showed the opposite pattern and ranged from 1.99 × 108 to 3.35 × 108copies/g. These findings enhance our understanding of the effect of increasing SO42- concentrations on organic carbon mineralization and could enhance the accuracy of assessments of greenhouse gas emissions in eutrophic lakes.

Severe cyanobacteria accumulation potentially induces methylotrophic methane producing pathway in eutrophic lakes.

Although cyanobacteria blooms lead to an increase in methane (CH4) emissions in eutrophic lakes have been intensively studied, the methane production pathways and driving mechanisms of the associated CH4 emissions are still unclear. In this study, the hypereutrophic Lake Taihu, which has extreme cyanobacteria accumulation, was selected to test hypothesis of a potential methylotrophic CH4 production pathway. Field observation displayed that the CH4 emission flux from the area with cyanobacteria accumulation was 867.01 µg m-2·min-1, much higher than the flux of 3.44 µg m-2·min-1 in the non-cyanobacteria accumulation area. The corresponding abundance of methane-producing archaea (MPA) in the cyanobacteria-concentrated area was 77.33% higher than that in the non-concentrated area via RT-qPCR technologies. Synchronously, sediments from these areas were incubated in anaerobic bottles, and results exhibited the high CH4 emission potential of the cyanobacteria concentrated area versus the non-concentrated area (1199.26 vs. 205.76 µmol/L) and more active biological processes (CO2 emission, 2072.8 vs. -714.62 µmol/L). We also found evidence for the methylotrophic methane producing pathway, which contributed to the high CH4 emission flux from the cyanobacteria accumulation area. Firstly, cyanobacteria decomposition provided the prerequisite of abundant methyl thioether substances, including DMS, DMDS, and DMTS. Results showed that the content of methyl thioethers increased with the biomass of cyanobacteria, and the released DMS, DMDS, and DMTS was up to 96.35, 3.22 and 13.61 µg/L, respectively, in the highly concentrated 25000 g/cm3 cyanobacteria treatment. Then, cyanobacteria decomposition created anaerobic microenvironments (DO 0.06 mg/L and Eh -304.8Mv) for methylotrophic methane production. Lastly, the relative abundance of Methanosarcinales was increased from 7.67% at the initial stage to 36.02% at the final stage within a sediment treatment with 10 mmol/L N(CH3)3. Quantitatively, the proportion of the methylotrophic methane production pathway was as high as 32.58%. This finding is crucial for accurately evaluating the methane emission flux, and evaluating future management strategies of eutrophic lakes.

Thermal degradation of xylan-based hemicellulose under oxidative atmosphere.

Xylan-based hemicellulose sample is tested in TG-MS under He, 7% O2, 20% O2 and 60% O2, in order to underpin the understanding of thermo-degradation mechanism of hemicellulose and biomass. The mass loss history recorded by TG can be divided into two main stages: (1) low-temperature stage with the peak located at around 265°C associated with thermal cracking of hemicellulose, and (2) high-temperature stage with the peak enhanced and shifted to lower temperatures by oxygen concentration ascribed to char combustion. A number of prominently evolved ions identified by MS can be designated to acetone, acetic acid, furfural, water, CO, CO2 and so on. The releasing profile of smaller fragments (water, CO and CO2) follows the pattern of DTG curve under different oxygen concentrations (especially for that in the high temperature stage). A three-step consecutive kinetic model employing "n-order reaction function" is proposed and achieved good fit for the experimental mass loss data of thermo-oxidation of hemicellulose.