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2-Phenoxyethanol (PhE) is an amphiphilic organic compound frequently used as a broad-spectrum preservative in cosmetic products and other consumer goods. PhE is also used as a biocidal component in occupational settings. A previous volunteer study by our working group following oral exposure to PhE showed that PhE is almost completely taken up into the human body followed by an extensive metabolization and fast urinary elimination. However, with respect to the importance of transdermal uptake, we now conducted another volunteer study applying dermal PhE exposure: five volunteers were dermally exposed with 0.4 mg/kg body weight of PhE each on a specified 800 cm 2 skin area using non-occlusive conditions. Subsequently, blood and urine samples were collected up to 48 h post-exposure. The present study illustrates the fast transdermal uptake of PhE. Following systemic resorption, PhE was extensively metabolized and rapidly eliminated in urine mainly in form of the metabolites PhAA (phenoxyacetic acid) and 4-OH-PhAA (4-hydroxyphenoxyacetic acid) accounting together for over 99% of the renally excreted PhE dose. The absolute urinary recovery rate of PhE was observed to be significantly lower following dermal exposure compared to oral uptake indicating a dermal resorption rate of PhE of about 45% in humans. The present study provides for the first time detailed insights into human biotransformation and toxicokinetics of PhE after dermal exposure, thus establishing a reliable strategy for human biomonitoring of PhE. The here presented results may thus be useful for further toxicokinetic modeling and forward dosimetry.

Plastics, including poly(ethylene terephthalate) (PET), possess many desirable characteristics and thus are widely used in daily life. However, non-biodegradability, once thought to be an advantage offered by plastics, is causing major environmental problem. Recently, a PET-degrading bacterium, Ideonella sakaiensis , was identified and suggested for possible use in degradation and/or recycling of PET. However, the molecular mechanism of PET degradation is not known. Here we report the crystal structure of I. sakaiensis PETase ( Is PETase) at 1.5 Å resolution. Is PETase has a Ser–His-Asp catalytic triad at its active site and contains an optimal substrate binding site to accommodate four monohydroxyethyl terephthalate (MHET) moieties of PET. Based on structural and site-directed mutagenesis experiments, the detailed process of PET degradation into MHET, terephthalic acid, and ethylene glycol is suggested. Moreover, other PETase candidates potentially having high PET-degrading activities are suggested based on phylogenetic tree analysis of 69 PETase-like proteins. Poly(ethylene terephthalate) (PET) is a widely used plastic and its accumulation in the environment has become global problem. Here the authors report the crystal structure of a Ideonella sakaiensis PET-degrading enzyme and propose a molecular mechanism for PET degradation.

•PCV13 is currently provided in SDS which has implications for cold chain requirements.•PCV13 in a multidose vial (MDV) is formulated with the preservative 2-phenoxyethanol.•Comparison of safety and immunogenicity of MDV with SDS was therefore required.•MDV was found safe and noninferior to SDS for all 13 pneumococcal serotypes.•PCV13 MDV can help optimize vaccination in resource-limited settings. This open-label randomized controlled trial in infants compared safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated with the preservative 2-phenoxyethanol (2-PE) in a multidose vial (MDV) to the current PCV13 without 2-PE in a single-dose syringe (SDS). Gambian infants were randomized 1:1 to receive PCV13 as either MDV or SDS at ages 2, 3, and 4months. Serotype-specific antipneumococcal antibody responses and opsonophagocytic activity ([OPA]; subset) were measured at age 5months. Noninferiority was declared if the lower bound of the 97.5% CI for the difference (MDV-SDS) in proportions of subjects achieving IgG concentrations ≥0.35μg/mL (primary endpoint) was greater than −10%. IgG geometric mean concentrations (GMCs) were noninferior if the lower limit of the two-sided 97.5% CI of the geometric mean ratio (MDV vs SDS) was greater than 0.5. Reactogenicity and other adverse events were collected. 500 participants were randomized and vaccinated; 489 (MDV: n=245; SDS: n=244) completed the trial. Noninferiority of MDV was demonstrated for all serotypes as measured by percentage of subjects achieving antibody responses above ≥0.35μg/mL. IgG GMCs (coprimary endpoint) also demonstrated noninferiority of MDV; OPA results supported these findings. Safety and tolerability were comparable between groups. PCV13 in MDV was safe and immunogenic when administered according to the routine schedule to infants. MDV was noninferior to SDS for all 13 pneumococcal serotypes. Comparable immunogenicity and safety profiles of PCV13 MDV and SDS suggest PCV13 MDV can help optimize vaccination in resource-limited settings. ClinicalTrials.gov NCT01964716 https://clinicaltrials.gov/ct2/show/NCT01964716.

Small solutes affect protein and nucleic acid processes because of favorable or unfavorable chemical interactions of the solute with the biopolymer surface exposed or buried in the process. Large solutes also exclude volume and affect processes where biopolymer molecularity and/or shape changes. Here, we develop an analysis to separate and interpret or predict excluded volume and chemical effects of a flexible coil polymer on a process. We report a study of the concentration-dependent effects of the full series from monomeric to polymeric PEG on intramolecular hairpin and intermolecular duplex formation by 12-nucleotide DNA strands. We find that chemical effects of PEG on these processes increase in proportion to the product of the amount of DNA surface exposed on melting and the amount of PEG surface that is accessible to this DNA, and these effects are completely described by two interaction terms that quantify the interactions between this DNA surface and PEG end and interior groups. We find that excluded volume effects, once separated from these chemical effects, are quantitatively described by the analytical theory of Hermans, which predicts the excluded volume between a flexible polymer and a rigid molecule. From this analysis, we show that at constant concentration of PEG monomer, increasing PEG size increases the excluded volume effect but decreases the chemical interaction effect, because in a large PEG coil a smaller fraction of the monomers are accessible to the DNA. Volume exclusion by PEG has a much larger effect on intermolecular duplex formation than on intramolecular hairpin formation.

A heightened interest in (trans)dermal delivery is in part driven by the need to improve the existing skin therapies and also the demand for alternative routes of administration, notably for pharmaceutical actives with undesirable oral absorption characteristics. The premise of delivering difficult actives to the skin or via the skin however is weighed down by the barrier function properties of the stratum corneum. Short of disrupting the skin by physical means, scientists have resorted to formulation with excipients known to enhance the skin penetration and permeation of drugs. A vehicle that has emerged over the years as a safe solubilizer and enhancer for a broad range of drug actives is the highly purified NF/EP grade of diethylene glycol monoethyl ether (DEGEE) commercially known as Transcutol®. Whereas numerous studies affirm its enhancing effect on drug solubilization, percutaneous absorption rate, and/or drug retention in the skin, there are few publications that unite the body of the published literature in describing the precise role and mechanisms of action for Transcutol®. In view of the current mechanistic understanding of skin barrier properties, this paper takes on a retrospective review of the published works and critically evaluates the data for potential misses due to experimental variables such as formulation design, skin model, skin hydration levels, and drug properties. The goal of this review is to mitigate the incongruence of the published works and to construct a unified, comprehensive understanding of how Transcutol® influences skin penetration and permeation. Graphical Abstract Transcutol has affinity for the hydrophilic head groups of the stratum corneum structures

In this paper, we report the synthesis of ZnO nanoparticles (NPs) by forced solvolysis of Zn(CH3COO)2·2H2O in alcohols with a different number of –OH groups. We study the influence of alcohol type (n-butanol, ethylene glycol and glycerin) on the size, morphology, and properties of the obtained ZnO NPs. The smallest polyhedral ZnO NPs (<30 nm) were obtained in n-butanol, while in ethylene glycol the NPs measured on average 44 nm and were rounded. Polycrystalline particles of 120 nm were obtained in glycerin only after water refluxing. In addition, here, we report the photocatalytic activity, against a dye mixture, of three model pollutants: methyl orange (MO), methylene blue (MB), and rhodamine B (RhB), a model closer to real situations where water is polluted with many chemicals. All samples exhibited good photocatalytic activity against the dye mixture, with degradation efficiency reaching 99.99%. The sample with smallest nanoparticles maintained a high efficiency >90%, over five catalytic cycles. Antibacterial tests were conducted against Gram-negative strains Salmonella enterica serovar Typhimurium, Pseudomonas aeruginosa, and Escherichia coli, and Gram-positive strains Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus, and Bacillus cereus. The ZnO samples presented strong inhibition of planktonic growth for all tested strains, indicating that they can be used for antibacterial applications, such as water purification.

The light-driven enzyme catalytic system composed of NAD(P)H regeneration and NAD(P)H-dependent enzymatic process emerges as a biomanufacturing platform for the synthesis of value-added chemicals, where the photo-responsive materials absorb solar energy to drive mass conversion. Herein, we report a photo-enzyme-membrane (PEM) catalytic system coupled with multi-enzyme cascade for ethylene glycol (EG) synthesis, in which membrane mediates energy transfer and mass conversion. Covalent organic polymer membrane as photo-membrane (PM) affords efficient NADH supply through synergistic intensification of electron transfer and proton transfer, where the bipyridine moiety mediates fast electron transfer from the generation site, and the sulfonic acid moiety facilitates proton transfer by enriching protons. Meanwhile, NADH-dependent enzyme is absorbed on PM followed by coating with a silica layer to form PEM, where the enzyme-bearing silica layer is defined as enzyme-membrane (EM). The enzymatic process is intensified by mitigating the adverse effects of PM on enzyme activity through precise regulation of EM thickness. Further, a dual-channel reactor is constructed for sustainable synthesis of EG with an initial synthesis rate of 2.43 mmol g PEM -1 h -1 by continuous supply of methanol. Our study offers an efficient and durable light-driven enzyme catalytic system for the synthesis of C 2+ from C 1 chemicals. The light-driven enzyme catalytic systems composed of NAD(P)H regeneration and NAD(P)H-dependent enzymatic process emerge as biomanufacturing platforms for the synthesis of value-added chemicals. Here, the authors present a photo-enzyme-membrane catalytic system coupled with multi-enzyme cascade for ethylene glycol synthesis.

Owing to the unique physical, chemical, mechanical and electrical properties, graphene and its derivatives have been extensively researched for diverse biomedical applications including in tissue engineering since the past decade. Tunable chemical functionalities of graphene oxide (GO), a graphene derivative, allow easy surface functionalization. Functionalization of GO with poly(ethylene glycol) (PEG) (PEG-GO) has received significant attention as it offers superior solubility, stability, and biocompatibility. Besides being an attractive candidate for drug delivery, PEG-GO can aid in the attachment, proliferation, and differentiation of stem cells, thereby augmenting tissue engineering. PEG-GO has shown excellent antibacterial efficacy, which could be an added advantage to minimize implant-associated infections. This review describes the synthesis techniques, properties, and biological potential of PEG-GO towards mammalian and bacterial cells. Studies wherein these nanomaterials have been explored for engineering various tissues are reviewed along with future opportunities in this field.

Deep eutectic solvents (DESs) have emerged as new promising solvents in the field of “green chemistry,” which possess a broad range of potential applications. However, the ecotoxicological profile of these solvents is still poorly known. In this study, ammonium-based deep eutectic solutions with glycerol (2:2), ethylene glycol (1:2), and diethylene glycol (1:2) as hydrogen bond donors in 1:2 proportion were evaluated for their interaction with various biological systems, including gram-positive and negative bacteria, fungi, fish, and human fibroblast cell lines. The DES synthesis was confirmed by Fourier transform infrared spectroscopy analysis, which analyses the interactions between DES precursors for their synthesis. The antimicrobial activity of tetrabutylammonium bromide: ethylene glycol was the most potent, while tetrabutylammonium bromide: diethylene glycol had a higher LC50 against C . carpio fish. Tetrabutylammonium bromide: glycerol was supposed to be the most suitable DES in terms of cell viability percentage (118%) and 2,2-diphenyl-1-picrylhydrazyl scavenging activity (93%). Finally, tetrabutylammonium bromide in glycerol can be considered an eco-friendly solvent due to its lower toxicity in both in vivo and in vitro environments.

The extreme durability of polyethylene terephthalate (PET) debris has rendered it a long-term environmental burden. At the same time, current recycling efforts still lack sustainability. Two recently discovered bacterial enzymes that specifically degrade PET represent a promising solution. First, Ideonella sakaiensis PETase, a structurally well-characterized consensus α/β-hydrolase fold enzyme, converts PET to mono-(2-hydroxyethyl) terephthalate (MHET). MHETase, the second key enzyme, hydrolyzes MHET to the PET educts terephthalate and ethylene glycol. Here, we report the crystal structures of active ligand-free MHETase and MHETase bound to a nonhydrolyzable MHET analog. MHETase, which is reminiscent of feruloyl esterases, possesses a classic α/β-hydrolase domain and a lid domain conferring substrate specificity. In the light of structure-based mapping of the active site, activity assays, mutagenesis studies and a first structure-guided alteration of substrate specificity towards bis-(2-hydroxyethyl) terephthalate (BHET) reported here, we anticipate MHETase to be a valuable resource to further advance enzymatic plastic degradation. Plastic polymer PET degrading enzymes are of great interest for achieving sustainable plastics recycling. Here, the authors present the crystal structures of the plastic degrading bacterial enzymes PETase, MHETase in its apo-form and MHETase bound to a non-hydrolyzable substrate analog.