Abstract
TP53
, a critical tumour suppressor gene, is mutated in over half of all cancers resulting in mutant-p53 protein accumulation and poor patient survival. Therapeutic strategies to target ...mutant-p53 cancers are urgently needed. We show that accumulated mutant-p53 protein suppresses the expression of
SLC7A11
, a component of the cystine/glutamate antiporter, system x
C
−
, through binding to the master antioxidant transcription factor NRF2. This diminishes glutathione synthesis, rendering mutant-p53 tumours susceptible to oxidative damage. System x
C
−
inhibitors specifically exploit this vulnerability to preferentially kill cancer cells with stabilized mutant-p53 protein. Moreover, we demonstrate that
SLC7A11
expression is a novel and robust predictive biomarker for APR-246, a first-in-class mutant-p53 reactivator that also binds and depletes glutathione in tumours, triggering lipid peroxidative cell death. Importantly, system x
C
−
antagonism strongly synergizes with APR-246 to induce apoptosis in mutant-p53 tumours. We propose a new paradigm for targeting cancers that accumulate mutant-p53 protein by inhibiting the SLC7A11–glutathione axis.
Ni‐based catalysts prepared through impregnation of depleted uranium oxides (DU) have successfully been employed as highly efficient, selective, and durable systems for CO2 hydrogenation to ...substituted natural gas (SNG; CH4) under an autothermal regime. The thermo‐physical properties of DU and the unique electronic structure of f‐block metal‐oxides combined with a nickel active phase, generated an ideal catalytic assembly for turning waste energy back into useful energy for catalysis. In particular, Ni/UOx stood out for the capacity of DU matrix to control the extra heat (hot‐spots) generated at its surface by the highly exothermic methanation process. At odds with the benchmark Ni/γ‐Al2O3 catalyst, the double action played by DU as a “thermal mass” and “dopant” for the nickel active phase unveiled the unique performance of Ni/UOx composites as CO2 methanation catalysts. The ability of the weakly radioactive ceramic (UOx) to harvest waste heat for more useful purposes was demonstrated in practice within a rare example of a highly effective and long‐term methanation operated under autothermal regime (i. e., without any external heating source). This finding is an unprecedented example that allows a real step‐forward in the intensification of “low‐temperature” methanation with an effective reduction of energy wastes. At the same time, the proposed catalytic technology can be regarded as an original approach to recycle and bring to a second life a less‐severe nuclear by‐product (DU), providing a valuable alternative to its more costly long‐term storage or controlled disposal.
Sustainable energy technology: Ni/UOx catalysts feature outstanding and durable methanation performance under exceptionally low‐temperature conditions or autothermal regime. A weakly radioactive nuclear by‐product (UOx) is engaged for the hot‐spots control in a highly exothermic process while converting extra‐heat into useful energy for promoting the chemoselective CO2‐to‐CH4 transformation.
In this work, we joined highly Ni‐loaded γ‐Al2O3 composites, straightforwardly prepared by impregnation methods, with an induction heating setup suited to control, almost in real‐time, any ...temperature swing at the catalyst sites (i. e., “hot spots” ignition) caused by an exothermic reaction at the heart of the power‐to‐gas (P2G) chain: CO2 methanation. We have shown how the combination of a poor thermal conductor (γ‐Al2O3) as support for large and highly interconnected nickel aggregates together with a fast heat control of the temperature at the catalytic bed allow part of the extra‐heat generated by the reaction exothermicity to be reused for maintaining the catalyst under virtual isothermal conditions, hence reducing the reactor power supply. Most importantly, a highly efficient methanation scheme for substitute natural gas (SNG) production (XCO2
up 98 % with >99 % SCH4
) under operative temperatures (150–230 °C) much lower than those commonly required with traditional heating setup has been proposed. As far as sustainable and environmental issues are concerned, this approach re‐evaluates industrially attractive composites (and their large‐scale preparation methods) for application to key processes at the heart of P2G chain while providing robust catalysts for which risks associated to nano‐objects leaching phenomena are markedly reduced if not definitively suppressed.
Multifunction composites: We propose a low‐temperature radiofrequency‐heated CO2 methanation scheme based on highly Ni‐loaded γ‐Al2O3 composites. These composites act as electrically conductive/magnetic susceptors for the induction heating technology while serving as robust catalysts for low‐temperature CO2 methanation.
Abstract Background We systematically reviewed the literature on the use of surgery, stereotactic ablative body radiotherapy (SABR) and percutaneous catheter ablation (PCA) techniques for the ...treatment of adrenal metastases to develop evidence-based recommendations. Methods A systematic review of the MEDLINE database was performed using structured search terms following PRISMA guidelines. Eligible publications were those published from 1990 to 2012, written in English, had at least five patients treated for adrenal metastasis and reported on patient clinical outcomes (local control, survival and treatment related complications/toxicity). Where possible, pooled 2-year local control and overall survival outcomes were analysed. Results Our search strategy produced a total of 45 papers addressing the three modalities – 30 adrenalectomy, nine SABR and six PCA (818, 178 and 51 patients, respectively). There was marked heterogeneity in outcome reporting, patient selection and follow-up periods between studies. The weighted 2-year local control and overall survival for adrenalectomy were 84% and 46%, respectively, compared with 63% and 19%, respectively for the SABR cohort. Only one study of PCA with five patients analysed clinical outcomes, reporting an actuarial local control of 80% at 1 year. Treatment related complications/toxicities were inconsistently reported. Conclusion There is insufficient evidence to determine the best local treatment modality for isolated or limited adrenal metastases from any primary tumour. Published data suggests adrenalectomy to be a reasonable treatment approach for isolated adrenal metastasis in suitable patients. SABR is a valid alternative in cases when surgery is not feasible or the operative risk is unacceptable. PCA cannot be recommended until there are more robust studies which include long-term oncological outcomes.
Invited for this month's cover are collaborating teams from academia—the French ICPEES and IS2M of Centre national de la recherche scientifique (CNRS) and the Italian ICCOM of Consiglio Nazionale ...delle Ricerche (CNR)—and industry with the participation of the ORANO group. The cover picture shows a CO2‐to‐CH4 process promoted by nickel nanoparticles supported on depleted uranium oxide under exceptionally low temperature values or autothermal conditions. The Research Article itself is available at 10.1002/cssc.202201859.
“At the same time, they give a second life to a less severe nuclear by‐product…” This and more about the story behind the research that inspired the Cover image is presented in the Cover Profile. Read the full text of the corresponding research at 10.1002/cssc.202201859. View the Front Cover here: 10.1002/cssc.202300237.
•Synthesis of N-CNTs/SiC composite with controlled macroscopic shape.•High effective surface area and low diffusion pathway.•Metal-free catalyst for the partial oxidation of H2S into elemental ...sulfur.•High activity and stability as a function of time on stream.
Hierarchical metal-free catalyst based on the CVD synthesis of nitrogen-doped carbon nanotubes decorated silicon carbide (N-CNTs/SiC) macroscopic host structure has been prepared. The catalyst was evaluated in the partial oxidation of H2S by oxygen into elemental sulfur in a fixed-bed reactor. The catalytic results indicate that the N-CNTs/SiC catalyst exhibits an extremely high desulfurization performance even under severe reaction conditions such as low temperature, high space velocity and at low O2-to-H2S molar ratio. The high desulfurization performance was attributed to the high effective surface area of the catalyst along with a short diffusion length associated with the nanoscopic dimension of the carbon nanotubes. The N-CNTs/SiC catalyst also displays a high stability as a function of time on stream which could be attributed to the strong anchoring of the nitrogen doping within the carbon matrix. The extrudates shape of the SiC support allows the direct macroscopic shaping of the catalyst for use in conventional fixed-bed reactor without facing problems linked with catalyst handling, transportation and pressure drop across the catalyst bed as encountered with nanoscopic carbon-based catalyst.
The effects of treatment processes on estrogenicity were evaluated by examining estradiol equivalent (EEQ) concentrations in influents and effluents of sewage treatment plants (STPs) located along ...Yeongsan and Seomjin rivers in Korea. The occurrence and distribution of estrogenic chemicals were also estimated for surface water in Korea and compared with seven other Asian countries including Laos, Cambodia, Vietnam, China, Indonesia, Thailand and Malaysia. Target compounds were nonylphenol (NP), octylphenol (OP), bisphenol A (BPA), estrone (E1), 17β-estradiol (E2), 17α-ethynylestradiol (EE2) and genistein (Gen). Water samples were pretreated and analyzed by liquid–liquid extraction (LLE) and gas chromatography/mass spectrometry (GC/MS). The results showed that the treatment processes of Korean STPs were sufficient to reduce the estrogenic activity of municipal wastewater. The concentrations of phenolic xenoestrogens (i.e., NP, OP and BPA) in samples of Yeongsan and Seomjin rivers were smaller than those reported by previous studies in Korea. In most samples taken from the seven Asian countries, the presence of E2 and EE2 was a major contributor toward estrogenic activity. The EEQ concentrations in surface water samples of the seven Asian countries were at a higher level in comparison to that reported in European countries, America and Japan. However, further studies with more sampling frequencies and sampling areas should be carried out for better evaluation of the occurrence and distribution of estrogenic compounds in these Asian countries.
In bio-based fermentation, the overall bioprocess efficiency is significantly affected by the metabolic burden associated with the expression of complete biosynthetic pathway as well as precursor and ...cofactor generating enzymes into a single microbial cell. To attenuate such burden by compartmentalizing the enzyme expression, recently synthetic biologists have used coculture or poly-culture techniques for biomolecules synthesis. In this paper, coculture system of two metabolically engineered
Escherichia coli
populations were employed which comprises upstream module expressing two enzymes converting
para
-coumaric acid into resveratrol and the downstream module expressing glucosyltransferase to convert the resveratrol into its glucosidated forms; polydatin and resveratroloside. Upon optimization of the initial inoculum ratio of two
E. coli
populations, 92 mg resveratrol glucosides/L (236 µM) was produced i.e. achieving 84% bioconversion from 280 µM of
p
-coumaric acid in 60 h by 3 L fed batch fermentor. This is the report of applying coculture system to produce resveratrol glucosides by expressing the aglycone formation pathway and sugar dependent pathway into two different cells.
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