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•We have studied the removal of diclofenac using an US/persulfate system.•The role played by various intermediate oxidative species were evaluated.•Different reaction intermediates ...were identified.•The possibly reaction pathway was discussed.•The influences of different operating conditions were studied.
Degradation of a diclofenac aqueous solution was performed using persulfate anions activated by ultrasound. The objective of this study was to analyze different parameters affecting the diclofenac (DCF) removal reaction by the ultrasonic persulfate (US/PS) process and to evaluate the role played by various intermediate oxidative species such as hydroxyl- and sulfate radicals, superoxide radical anion or singlet oxygen in the removal process as well as to determine a possible reaction pathway. The effects of pH, initial persulfate anion concentration, ultrasonic amplitude and temperature on DCF degradation were examined. Sulfate and hydroxyl radicals were involved in the main reaction pathway of diclofenac. Diclofenac amide and three hydroxy-diclofenac isomers (3´-hydroxy diclofenac, 4´-hydroxy diclofenac and 5-hydroxy diclofenac) were identified as reaction intermediates.
Carriers containing multiple compartments have recently emerged as a new platform with enormous potential in the fields of drug delivery and cell mimicry.
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•Multicompartment carriers ...have emerged as a new platform for biomedical applications.•We review architectures based on liposomes, polymersomes and polymer capsules.•Special emphasis is put in the field of drug delivery and therapeutic cell mimicry.
Compartmentalization is a key feature of biological cells which conduct their metabolic activity in individual steps isolated in distinct, separated compartments. The creation of architectures containing multiple compartments with a structure that resembles that of a biological cell has generated significant research attention and these assemblies are proposed as candidate materials for a range of biomedical applications. In this Review article, the recent successes of multicompartment architectures as carriers for the delivery of therapeutic cargo or the creation of micro- and nanoreactors that mimic metabolic activities, thus acting as artificial cells or organelles, are discussed. The developed technologies to assemble such complex architectures are outlined, the multicompartment carriers’ properties which contribute to their performance in diverse applications are discussed, and their successful applications are highlighted. Finally, future directions and developments in the field are suggested.
•Thermal storage using powders are hindered by the lack of powder flowability.•Two critical factors governing flowability are temperature and consolidation.•Powder cohesiveness has been measured for ...different powders.•Powder cohesiveness is enhanced with temperature and consolidation.•Nanosilica coating helps mitigating the loss of powder flowability.
Solar technology has shown a keen interest in thermochemical storage to extend its operational timespan beyond a daily basis. Thermochemical solutions are operated by fine powders. Unlike regular granular media, fine powders become cohesive. However, despite the paramount importance of controlling powder flowability to integrate these solutions in solar technology, little research has focused on how powder cohesiveness shapes the flow regime through the storage circuit. This paper investigates two critical factors governing the granular flow through the storage route: temperature and consolidation. The experimental setup emulates the transition powders undergo from silos to reactors. Powders were consolidated before being fluidized at a given temperature, ranging from ambient to 500 °C. Tensile yield strength was then measured for different powders. The results exhibit the expected rising trend in the tensile yield strength of powders as temperature increases. But, interestingly, tensile yield strength skyrocketed when powders were subjected to higher consolidations. Backed by theoretical estimations based on mechanical models, the analysis unveils a cross effect between temperature and consolidation. A combined action that reinforces cohesion by promoting a plastic deformation; worsening, thus, powder flowability. In conclusion, consolidation introduces a multiplying effect on the powder cohesiveness as temperature increases, which represents a serious caveat to solar energy storage technology. To mitigate potential flowability issues, this work explores the use of nanoparticles of silica to layer limestone (calcium carbonate, CaCO3) particles. The nanosilica coatings turned out to be a very promising solution to preclude the enhancement of cohesion induced at high temperatures. Coated samples showed powder cohesiveness at high temperatures similar to the values obtained at room temperature. A solution that offers a simple and reliable alternative to smooth the flow regime in solid-based energy storage technologies at production environments.
There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status ...measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC.
We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial).
In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS hazard ratio (HR), 3.98; 95% CI 1.74–9.10; P < 0.001 and HR 3.81; 95% CI 2.28–6.37; P < 0.001, respectively, PFS (HR 2.18; 95% CI 1.08–4.39; P = 0.03, and HR 1.95; 95% CI 1.23–3.11; P = 0.01, respectively) and rate of PSA decline≥50% odds ratio (OR), 4.7; 95% CI 1.17–19.17; P = 0.035 and OR, 5.0; 95% CI 1.70–14.91; P = 0.003, respectively. AR mutations 2105T>A (p.L702H) and 2632A>G (p.T878A) were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47–not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94–9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26–19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16–56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts.
Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required.
NCT02288936 (PREMIERE trial).
Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy leading to severe metabolic disturbances in infants, which recover spontaneously after 6‐months of age. ...RIRCD is associated with the homoplasmic m.14674T>C mitochondrial DNA mutation; however, only ~ 1/100 carriers develop the disease. We studied 27 affected and 15 unaffected individuals from 19 families and found additional heterozygous mutations in nuclear genes interacting with mt‐tRNAGlu including EARS2 and TRMU in the majority of affected individuals, but not in healthy carriers of m.14674T>C, supporting a digenic inheritance. Our transcriptomic and proteomic analysis of patient muscle suggests a stepwise mechanism where first, the integrated stress response associated with increased FGF21 and GDF15 expression enhances the metabolism modulated by serine biosynthesis, one carbon metabolism, TCA lipid oxidation and amino acid availability, while in the second step mTOR activation leads to increased mitochondrial biogenesis. Our data suggest that the spontaneous recovery in infants with digenic mutations may be modulated by the above described changes. Similar mechanisms may explain the variable penetrance and tissue specificity of other mtDNA mutations and highlight the potential role of amino acids in improving mitochondrial disease.
Synopsis
Reversible infantile respiratory chain deficiency (RIRCD) is a rare mitochondrial myopathy associated with homoplasmic mutation in mt‐tRNAGlu. Heterozygous mutations in nuclear genes interacting with mt‐tRNAGlu induce the integrated stress response (ISR) and metabolic rearrangements that reduce penetrance and promote spontaneous RIRCD recovery in infants.
Nuclear gene variants that affect glutamate/glutamine metabolism or mt‐tRNAGlu aminoacylation contribute to manifestation of RIRCD, when co‐occurring with the mtDNA m.14674T>C variant.
Analysis of diseased muscles reveals that recovery from RIRCD occurs in a stepwise manner in infants.
During phase one, ISR signaling increases FGF21 and GDF15 expression and enhances lipid and amino acid metabolism.
In a second phase, patients present activation of mTOR, leading to increased mitochondrial biogenesis.
ISR and increased mitochondria number facilitate a metabolic shift that improves amino acid availability and contribute to the spontaneous recovery in phase three.
Heterozygous mutations in nuclear genes interacting with mt‐tRNAGlu induce the integrated stress response and metabolic rearrangements, reducing penetrance and promoting spontaneous recovery in a rare mitochondrial myopathy.
The intermediate filament (IF) cytoskeleton has been proposed to regulate morphogenic processes by integrating the cell fate signaling machinery with mechanical cues. Signaling between endothelial ...cells (ECs) and vascular smooth muscle cells (VSMCs) through the Notch pathway regulates arterial remodeling in response to changes in blood flow. Here we show that the IF-protein vimentin regulates Notch signaling strength and arterial remodeling in response to hemodynamic forces. Vimentin is important for Notch transactivation by ECs and vimentin knockout mice (VimKO) display disrupted VSMC differentiation and adverse remodeling in aortic explants and in vivo. Shear stress increases Jagged1 levels and Notch activation in a vimentin-dependent manner. Shear stress induces phosphorylation of vimentin at serine 38 and phosphorylated vimentin interacts with Jagged1 and increases Notch activation potential. Reduced Jagged1-Notch transactivation strength disrupts lateral signal induction through the arterial wall leading to adverse remodeling. Taken together we demonstrate that vimentin forms a central part of a mechanochemical transduction pathway that regulates multilayer communication and structural homeostasis of the arterial wall.
Aims
The aim of the study was to isolate bacterial lignin‐degrading bacteria from municipal solid waste (MSW) soil, and to investigate whether they could be used to delignify ...lignocellulose‐containing soil, and enhance methane release.
Methods and Results
A set of 20 bacterial lignin degraders, including 11 new isolates from MSW soil, were tested for delignification and phenol release in soil containing 1% pine lignocellulose. A group of seven strains were then tested for enhancement of gas release from soil containing 1% lignocellulose in small‐scale column tests. Using an aerobic pretreatment, aerobic strains such as Pseudomonas putida showed enhanced gas release from the treated sample, but four bacterial isolates showed 5–10‐fold enhancement in gas release in an in situ experiment under microanaerobic conditions: Agrobacterium sp., Lysinibacillus sphaericus, Comamonas testosteroni and Enterobacter sp.
Conclusions
The results show that facultative anaerobic bacterial lignin degraders found in landfill soil can be used for in situ delignification and enhanced gas release in soil containing lignocellulose.
Significance and Impact of the Study
The study demonstrates the feasibility of using an in situ bacterial treatment to enhance gas release and resource recovery from landfill soil containing lignocellulosic waste.
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