Spinal muscular atrophy (SMA), a rare neuromuscular disorder, is the leading genetic cause of death in infants and toddlers. SMA is caused by the deletion or a loss of function mutation of the ...survival motor neuron 1 (SMN1) gene. In humans, a second closely related gene SMN2 exists; however it codes for a less stable SMN protein. In recent years, significant progress has been made toward disease modifying treatments for SMA by modulating SMN2 pre-mRNA splicing. Herein, we describe the discovery of LMI070/branaplam, a small molecule that stabilizes the interaction between the spliceosome and SMN2 pre-mRNA. Branaplam (1) originated from a high-throughput phenotypic screening hit, pyridazine 2, and evolved via multiparameter lead optimization. In a severe mouse SMA model, branaplam treatment increased full-length SMN RNA and protein levels, and extended survival. Currently, branaplam is in clinical studies for SMA.
Extra virgin olive oil (EVOO) is largely used in Mediterranean diet, and it is also worldwide apprised not only for its organoleptic properties but also for its healthy effects mainly attributed to ...the presence of several naturally occurring phenolic and polyphenolic compounds (bio‐phenols). These compounds are characterized by the presence of multiple phenolic groups in more or less complex structures. Their content is fundamental in defining the healthy qualities of EVOO and consequently the analytical methods for their characterization and quantification are of current interest. Traditionally their determination has been conducted using a colorimetric assay based on the reaction of Folin‐Ciocalteu (FC) reagent with the functional hydroxy groups of phenolic compounds. Identification and quantification of the bio‐phenols in olive oils requires certainly more performing analytical methods. Chromatographic separation is now commonly achieved by HPLC, coupled with spectrometric devices as UV, FID, and MS. This last approach constitutes an actual cutting‐edge application for bio‐phenol determination in complex matrices as olive oils, mostly on the light of the development of mass analyzers and the achievement of high resolution and accurate mass measurement in more affordable instrument configurations. After a short survey of some rugged techniques used for bio‐phenols determination, in this review have been described the most recent mass spectrometry‐based methods, adopted for the analysis of the bio‐phenols in EVOOs. In particular, the sample handling and the results of HPLC coupled with low‐ and high‐resolution MS and MS/MS analyzers, of ion mobility mass spectrometry and ambient mass spectrometry have been reported and discussed.
ZIF-67(zinc-methylimidazolate framework-67), one of the zeolitic imidazolate frameworks (ZIFs), was used for the removal of phenol from aqueous solutions via adsorption and shows high adsorption ...capacity for phenol. The thermodynamic and kinetic adsorption behavior of ZIF-67 for phenol in water with concentration ranging from 50 to 300 ppm were investigated in a batch reactor and a ZIF-67 packed column, respectively. The effects of pH, contact time, zeta potential of the adsorbent and temperature on the adsorption behavior were evaluated, and the results demonstrated that the adsorption is primarily brought about by a specific favorable interaction (electrostatic interaction) between phenol and ZIF-67 surface. The suitability of the Langmuir adsorption model to the equilibrium data was investigated for each phenol-adsorbent system, which the results showed that the equilibrium data for all the phenol-sorbent systems fitted the Langmuir model. Thermodynamic parameters such as Gibbs free energy are calculated from the experimental data at different temperatures. The adsorbent could be perfectly regenerated at 120 °C with little loss in the adsorption ability.
ZIF-67 performs high adsorption capacity for phenol from aqueous solutions and excellent reusability with simple thermal regeneration treatment. Display omitted
•ZIF-67 shows high adsorption capacity for phenol even though positivity was not high.•Solution pH have significant influence on the removal of phenol.•The removal of phenol by ZIF-67 fits pseudo-second order kinetic reaction law.•Used ZIF-67 can be recycled for the adsorption by simple thermal regeneration.•The ZIF-67 packed column shows excellent reusability for phenol adsorption even has been used two times.
Phenols and phenolic ethers are significant scaffolds recurring both in nature and among approved small-molecule pharmaceuticals. This compendium presents the first comprehensive compilation and ...analysis of the structures of U.S. FDA-approved molecules containing phenol or phenolic ether fragments. This dataset comprises 371 structures, which are strongly represented by natural products. A total of 55 of the compounds described here are on the World Health Organization’s list of essential medicines. Structural analysis reveals significant differences in the physicochemical properties imparted by phenols versus phenol ethers, each having benefits and drawbacks for drug developability. Despite trends over the past decade to increase the fraction of sp3 centers in drug leads, thereby “escaping flatland”, phenols and phenolic ethers are represented in 62% of small-molecule drugs approved in 2020, suggesting that this aromatic moiety holds a special place in drugs and natural products.
Anaerobic biodegradation of toxic compounds found in industrial wastewater is an attractive solution allowing the recovery of energy and resources but it is still challenging due to the low kinetics ...making the anaerobic process not competitive against the aerobic one. In this review, we summarise the present state of knowledge on the anaerobic biodegradation process for phenol, a typical target compound employed in toxicity studies on industrial wastewater treatment. The objective of this article is to provide an overview on the microbiological and technological aspects of anaerobic phenol degradation and on the research needs to fill the gaps still hindering the diffusion of the anaerobic process. The first part is focused on the microbiology and extensively presents and characterises phenol-degrading bacteria and biodegradation pathways. In the second part, dedicated to process feasibility, anaerobic and aerobic biodegradation kinetics are analysed and compared, and strategies to enhance process performance, i.e. advanced technologies, bioaugmentation, and biostimulation, are critically analysed and discussed. The final section provides a summary of the research needs. Literature data analysis shows the feasibility of anaerobic phenol biodegradation at laboratory and pilot scale, but there is still a consistent gap between achieved aerobic and anaerobic performance. This is why current research demand is mainly related to the development and optimisation of powerful technologies and effective operation strategies able to enhance the competitiveness of the anaerobic process. Research efforts are strongly justified because the anaerobic process is a step forward to a more sustainable approach in wastewater treatment.
Key points
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Review of phenol-degraders bacteria and biodegradation pathways.
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Anaerobic phenol biodegradation kinetics for metabolic and co-metabolic processes.
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Microbial and technological strategies to enhance process performance.
Graphical abstract
The activated bio-chars (AB) were successfully synthesized from rice husk by one- and two-step KOH-catalyzed pyrolysis. The two-step pyrolysis can produce the high yields of AB compared to the ...one-step pyrolysis. Moreover, the yield of AB decreased with the increase of the mass ratio of KOH and char, which had a significant effect on the development of the surface area and porosity of carbon. In particular, the AB derived from the two-step pyrolysis at 750°C (mass ratio of KOH and char was 3) had the highest specific surface area (SBET=2138m2/g) with many micro-porous structures, which was favored for the phenol adsorption. The maximum adsorption capacity of AB2-3-750 reached 201mg/g because of its excellent surface porosity property. The phenol can be efficiently removed from water by only several minutes. The Langmuir model defined well the adsorption isotherm with a high correlation coefficient value, indicating a monolayer adsorption behavior. And the adsorption process defined well with the pseudo-second-order model. The phenol molecules passed into the internal surface via the liquid-film controlled diffusion, so the behavior of phenol adsorption onto the AB was predominantly controlled via the chemisorption. Furthermore, the functional groups on the outer surfaces of AB can attract the phenol molecules onto the internal surfaces via “π-π dispersion interaction” and “donor-acceptor effect”.
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•Activated bio-chars were successfully synthesized by one- and two-step KOH-catalyzed pyrolysis.•Two-step pyrolysis can produce a higher yield of the activated bio-char.•The activated bio-char via the two-step pyrolysis at 750°C had a highest SBET=2138m2/g with many microporous structure.•The activated bio-chars can efficiently remove phenol from wastewater by several minutes.
The selective hydroxylation of benzene to phenol, without the formation of side products resulting from overoxidation, is catalyzed by cytochrome P450BM3 with the assistance of amino acid derivatives ...as decoy molecules. The catalytic turnover rate and the total turnover number reached 259 min−1 P450BM3−1 and 40 200 P450BM3−1 when N‐heptyl‐l‐proline modified with l‐phenylalanine (C7‐l‐Pro‐l‐Phe) was used as the decoy molecule. This work shows that amino acid derivatives with a totally different structure from fatty acids can be used as decoy molecules for aromatic hydroxylation by wild‐type P450BM3. This method for non‐native substrate hydroxylation by wild‐type P450BM3 has the potential to expand the utility of P450BM3 for biotransformations.
Amino acid derivatives, with structures that are totally different from those of fatty acids, efficiently activate cytochrome P450BM3 for the direct hydroxylation of benzene to phenol. The catalytic turnover rate and total turnover number reached 259 min−1 P450BM3−1 and 40 200 P450BM3−1, respectively.
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•Our method is a major improvement to the widely used Phenol–Sulfuric Acid method.•We avoided the health and environmental hazards associated with phenol use.•We developed a direct ...correlation of UV-absorbance to total carbon concentration.•We significantly reduce the waiting time prior to light absorption reading.•We differentiate between neutral and anionic carbohydrates absorbance.
A new UV spectrophotometry based method for determining the concentration and carbon content of carbohydrate solution was developed. This method depends on the inherent UV absorption potential of hydrolysis byproducts of carbohydrates formed by reaction with concentrated sulfuric acid (furfural derivatives). The proposed method is a major improvement over the widely used Phenol–Sulfuric Acid method developed by DuBois, Gilles, Hamilton, Rebers, and Smith (1956). In the old method, furfural is allowed to develop color by reaction with phenol and its concentration is detected by visible light absorption. Here we present a method that eliminates the coloration step and avoids the health and environmental hazards associated with phenol use. In addition, avoidance of this step was shown to improve measurement accuracy while significantly reducing waiting time prior to light absorption reading. The carbohydrates for which concentrations and carbon content can be reliably estimated with this new rapid Sulfuric Acid–UV technique include: monosaccharides, disaccharides and polysaccharides with very high molecular weight.
Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a ...gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.
Nickel (hydr)oxide (NiOH) is known to be good co-catalyst for the photoelectrochemical oxidation of water, and for the photocatalytic oxidation of organics on different semiconductors. Herein we ...report a greatly improved activity of Bi
MoO
(BMO) by nickel hexammine perchlorate (NiNH). Under visible light, phenol oxidation on BMO was slow. After NiNH, NiOH, and Ni
loading, a maximum rate of phenol oxidation increased by factors of approximately 16, 8.8, and 4.7, respectively. With a BMO electrode, all catalysts inhibited O
reduction, enhanced water (photo-)oxidation, and facilitated the charge transfer at solid-liquid interface, respectively, the degree of which was always NiNH > NiOH > Ni
. Solid emission spectra indicated that all catalysts improved the charge separation of BMO, the degree of which also varied as NiNH > NiOH > Ni
. Furthermore, after a phenol-free aqueous suspension of NiNH/BMO was irradiated, there was a considerable Ni(III) species, but a negligible NH
radical. Accordingly, a plausible mechanism is proposed, involving the hole oxidation of Ni(II) into Ni(IV), which is reactive to phenol oxidation, and hence promotes O
reduction. Because NH
is a stronger ligand than H
O, the Ni(II) oxidation is easier for Ni(NH
)
than for Ni(H
O)
. This work shows a simple route how to improve BMO photocatalysis through a co-catalyst.
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