From Bulk Molybdenum Disulfide (MoS2) to Suspensions of Exfoliated MoS2 in an Aqueous Medium and Their Applications.

Two-dimensional (2D) layered materials like graphene, transition-metal dichalcogenides (TMDs), boron nitrides, etc., exhibit unique and fascinating properties, such as high surface-to-volume ratio, inherent mechanical flexibility and robustness, tunable bandgap, and high carrier mobility, which makes them an apt candidate for flexible electronics with low consumption of power. Because of these properties, they are in tremendous demand for advancement in energy, environmental, and biomedical sectors developed through various technologies. The production and scalability of these materials must be sustainable and ecofriendly to utilize these unique properties in the real world. Here, in this current review, we review molybdenum disulfide (MoS2 nanosheets) in detail, focusing on exfoliated MoS2 in water and the applicability of aqueous MoS2 suspensions in various fields. The exfoliation of MoS2 results in the formation of single or few-layered MoS2. Therefore, this Review focuses on the few layers of exfoliated MoS2 that have the additional properties of 2D layered materials and higher excellent compatibility for integration than existing conventional Si tools. Hence, a few layers of exfoliated MoS2 are widely explored in biosensing, gas sensing, catalysis, photodetectors, energy storage devices, a light-emitting diode (LED), adsorption, etc. This review covers the numerous methodologies to exfoliate MoS2, focusing on the various published methodologies to obtain nanosheets of MoS2 from water solutions and their use.

Isotropic Gels of Cellulose Nanocrystals Grafted with Dialkyl Groups: Influence of Surface Group Topology from Nonlinear Oscillatory Shear.

Attractive (non-self-assembling) aqueous cellulose nanocrystal (CNC) suspensions were topologically tailored into isotropic gels through the surface grafting of dialkyl groups. We thus focus on the influence of CNC concentration, including for pristine CNC, surface linker branching, branching degree, and the influence of side group size and branch-on-branch surface-grafted groups. The resulting mobility and strength of interaction in particle-particle interaction mediated by the surface groups was investigated from a rheological point of view. The emphasis is on nonlinear material parameters from Fourier-transform rheology and stress decomposition analysis. The results show that nonlinear material parameters are more sensitive than linear viscoelastic parameters to the onset of weakly interconnected networks in pristine CNC isotropic suspensions. All surface-modified CNC suspensions resulted in isotropic gels. The nonlinear material parameters were found to be broadly sensitive to CNC concentration, branching, degree of branching and surface-grafted linkers' length. However, the length of the grafted chains and the degree of branching were the primary factors influencing the nonlinear material response. Furthermore, the results showed evidence of two strain amplitude ranges with distinct nonlinear signatures that could be attributed to the disruption of weak network connection points and to distortions of more dense (aggregate) network regions, respectively.

Kinetics of Periodate-Mediated Oxidation of Cellulose.

The oxidation of cellulose to dialdehyde cellulose (DAC) is a process that has received increased interest during recent years. Herein, kinetic modeling of the reaction with sodium periodate as an oxidizing agent was performed to quantify rate-limiting steps and overall kinetics of the cellulose oxidation reaction. Considering a pseudo-first-order reaction, a general rate expression was derived to elucidate the impact of pH, periodate concentration, and temperature on the oxidation of cellulose and concurrent formation of cellulose degradation products. Experimental concentration profiles were utilized to determine the rate constants for the formation of DAC (k1), degradation constant of cellulose (k2), and degradation of DAC (k3), confirming that the oxidation follows a pseudo-first-order reaction. Notably, the increase in temperature has a more pronounced effect on k1 compared to the influence of IO4- concentration. In contrast, k2 and k3 display minimal changes in response to IO4- concentration but increase significantly with increasing temperature. The kinetic model developed may help with understanding the rate-limiting steps and overall kinetics of the cellulose oxidation reaction, providing valuable information for optimizing the process toward a faster reaction with higher yield of the target product.

Nanostructures of etherified arabinoxylans and the effect of arabinose content on material properties.

To further our understanding of a thermoplastic arabinoxylan (AX) material obtained through an oxidation-reduction-etherification pathway, the role of the initial arabinose:xylose ratio on the material properties was investigated. Compression molded films with one molar substitution of butyl glycidyl ether (BGE) showed markedly different tensile behaviors. Films made from low arabinose AX were less ductile, while those made from high arabinose AX exhibited elastomer-like behaviors. X-ray scattering confirmed the presence of nanostructure formation resulting in nano-domains rich in either AX or BGE, from side chain grafting. The scattering data showed variations in the presence of ordered structures, nano-domain sizes and their temperature response between AX with different arabinose contents. In dynamic mechanical testing, three transitions were observed at approximately -90 °C, -50 °C and 80 °C, with a correlation between samples with more structured nano-domains and those with higher onset transition temperatures and lower storage modulus decrease. The mechanical properties of the final thermoplastic AX material can therefore be tuned by controlling the composition of the starting material.

Screening for phenotype selective activity in multidrug resistant cells identifies a novel tubulin active agent insensitive to common forms of cancer drug resistance.

BACKGROUND: Drug resistance is a common cause of treatment failure in cancer patients and encompasses a multitude of different mechanisms. The aim of the present study was to identify drugs effective on multidrug resistant cells. METHODS: The RPMI 8226 myeloma cell line and its multidrug resistant subline 8226/Dox40 was screened for cytotoxicity in response to 3,000 chemically diverse compounds using a fluorometric cytotoxicity assay (FMCA). Follow-up profiling was subsequently performed using various cellular and biochemical assays. RESULTS: One compound, designated VLX40, demonstrated a higher activity against 8226/Dox40 cells compared to its parental counterpart. VLX40 induced delayed cell death with apoptotic features. Mechanistic exploration was performed using gene expression analysis of drug exposed tumor cells to generate a drug-specific signature. Strong connections to tubulin inhibitors and microtubule cytoskeleton were retrieved. The mechanistic hypothesis of VLX40 acting as a tubulin inhibitor was confirmed by direct measurements of interaction with tubulin polymerization using a biochemical assay and supported by demonstration of G2/M cell cycle arrest. When tested against a broad panel of primary cultures of patient tumor cells (PCPTC) representing different forms of leukemia and solid tumors, VLX40 displayed high activity against both myeloid and lymphoid leukemias in contrast to the reference compound vincristine to which myeloid blast cells are often insensitive. Significant in vivo activity was confirmed in myeloid U-937 cells implanted subcutaneously in mice using the hollow fiber model. CONCLUSIONS: The results indicate that VLX40 may be a useful prototype for development of novel tubulin active agents that are insensitive to common mechanisms of cancer drug resistance.

Screening of hydrogen bonds in modified cellulose acetates with alkyl chain substitutions.

This study aimed to elucidate how the glass transition temperature and water interactions in cellulose esters are affected by the structures of their side chains. Cellulose acetate, cellulose acetate propionate and cellulose acetate butyrate with three fractions of butyrates, all having the same total degree of substitution, were selected, and hot-melt pressed. The degree of substitution, structural properties, and water interactions were determined. The Hansen solubility parameters were calculated and showed that the dispersive energy dominates the total cohesive energy, followed by hydrogen bonding and polar energy. The glass transition temperature (Tg) decreased, counter-intuitively, with an increased total cohesive energy, which can be explained by the short-range hydrogen bonds being screened by the increased length of the substituents. The solubility and penetration of water in the cellulose esters decreased with increased side chain length, although the hydrogen bonding energies for all the esters were approximately constant.

Side chains affect the melt processing and stretchability of arabinoxylan biomass-based thermoplastic films.

Hydrophobization of hemicellulose causes melt processing and makes them stretchable thermoplastics. Understanding how native and/or appended side chains in various hemicelluloses after chemical modification affect melt processing and material properties can help in the development of products for film packaging and substrates for stretchable electronics applications. Herein, we describe a one-step and two-step strategy for the fabrication of flexible and stretchable thermoplastics prepared by compression molding of two structurally different arabinoxylans (AX). For one-step synthesis, the n-butyl glycidyl ether epoxide ring was opened to the hydroxyl group, resulting in the introduction of alkoxide side chains. The first step in the two-step synthesis was periodate oxidation. Because the melt processability for AXs having low arabinose to xylose ratio (araf/xylp<0.5) have been limited, two structurally distinct AXs extracted from wheat bran (AXWB, araf/xylp = 3/4) and barley husk (AXBH, araf/xylp = 1/4) were used to investigate the effect of araf/xylp and hydrophobization on the melt processability and properties of the final material. Melt compression processability was achieved in AXBH derived samples. DSC and DMA confirmed that the thermoplastics derived from AXWB and AXBH had dual and single glass transition (Tg) characteristics, respectively, but the thermoplastics derived from AXBH had lower stretchability (maximum 160%) compared to the AXWB samples (maximum 300%). Higher araf/xylp values, and thus longer alkoxide side chains in AXWB-derived thermoplastics, explain the stretchability differences.

Sunlight promoted removal of toxic hexavalent chromium by cellulose derived photoactive carbon dots.

A scalable synthetic procedure for fabricating photoactive carbon dots (CD) from microcrystalline cellulose (MCC) is presented. The MCC was transformed into a photoactive nanosized CD by a one-step acid-assisted thermal-carbonization (~90 °C for 30 min). The efficiency of the obtained CD was determined by photo-removal of toxic hexavalent chromium (Cr(VI)) ions from wastewater. CD obtained from cellulose completely removed 20 ppm of Cr(VI) wastewater within ∼120 min under sunlight illumination. No Cr(VI) removal was observed in dark conditions and with control cellulose material as reference samples. The Cr(VI) removal follows pseudo-first-order kinetics along with a half-life of ∼26 min. Furthermore, the Cr(VI) removal from wastewater was supported via cyclic voltammetry analysis. Using a low-cost, naturally available cellulose material and sulfuric acid, the world's most-used chemical, creates techno-economic prerequisites for a scalable process of photoactive carbon dots.

Diphenylthiourea, a common rubber chemical, is bioactivated to potent skin sensitizers.

Diphenylthiourea (DPTU) is a known skin sensitizer commonly used as a vulcanization accelerator in the production of synthetic rubber, for example, neoprene. The versatile usage of neoprene is due to the multifaceted properties of the material; for example, it is stretchable, waterproof, and chemical- and abrasion-resistant. The wide application of neoprene has resulted in numerous case reports of dermatitis patients allergic to DPTU. The mechanism by which DPTU works as a contact allergen has not been described; thus, the aim of the present study was to investigate if DPTU is a prohapten that can be activated by skin metabolism. The metabolic activation and covalent binding of (14)C-labeled DPTU to proteins were tested using a skinlike cytochrome P450 (P450) cocktail containing the five most abundant P450s found in human skin (CYP1A1, 1B1, 2B6, 2E1, and 3A5) and human liver microsomes. The incubations were carried out in the presence or absence of the metabolite trapping agents glutathione, methoxylamine, and benzylamine. The metabolism mixtures were analyzed by LC-radiochromatography, LC-MS, and LC-MS/MS. DPTU was mainly metabolically activated to reactive sulfoxides resulting in desulfurated adducts in both enzymatic systems used. Also, phenylisothiocyanate and phenylisocyanate were found to be metabolites of DPTU. The sensitizing capacity of the substrate (DPTU) and three metabolites was tested in the murine local lymph node assay. Two out of three metabolites tested were strong skin sensitizers, whereas DPTU itself, as previously known, was negative using this mouse model. In conclusion, DPTU forms highly reactive metabolites upon bioactivation by enzymes present in the skin. These metabolites are able to induce skin sensitization and are probable causes for DPTU allergy. To increase the possibilities of diagnosing contact allergy to DPTU-containing items, we suggest that suitable metabolites of DPTU should be used for screening testing.

Hydrophobization of arabinoxylan with n-butyl glycidyl ether yields stretchable thermoplastic materials.

Hemicelluloses are regarded as one of the first candidates for the development of value-added materials due to their renewability, abundance, and functionality. However, because most hemicelluloses are brittle, they can only be processed as a solution and cannot be processed using industrial melt-based polymer processing techniques. In this study, arabinoxylan (AX) was hydrophobized by incorporating butyl glycidyl ether (BuGE) into the hydroxyl groups through the opening of the BuGE epoxide ring, yielding alkoxy alcohols with terminal ethers. The formed BuGE derivatives were melt processable and can be manufactured into stretchable thermoplastic films through compression molding, which has never been done before with hemicellulose modified in a single step. The structural and thermomechanical properties of the one-step synthesis approach were compared to those of a two-step synthesis with a pre-activation step to demonstrate its robustness. The strain at break for the one-step synthesized AX thermoplastic with 3 mol of BuGE is ≈200%. These findings suggest that thermoplastic polymers can be composited with hemicelluloses or that thermoplastic polymers made entirely of hemicelluloses can be designed as packaging and stretchable electronics supports.

Oxidation Level and Glycidyl Ether Structure Determine Thermal Processability and Thermomechanical Properties of Arabinoxylan-Derived Thermoplastics.

Developing flexible, stretchable, and thermally processable materials for packaging and stretchable electronic applications from polysaccharide-based polymers contributes to the smooth transition of the fossil-based economy to the circular bioeconomy. We present arabinoxylan (AX)-based thermoplastics obtained by ring-opening oxidation and subsequent reduction (dA-AX) combined with hydrophobization with three different glycidyl ethers [n-butyl (BuGE), isopropyl (iPrGE), and 2-ethyl hexyl (EtHGE) glycidyl ether]. We also investigate the relationship between structural composition, thermal processing, and thermomechanical properties. BuGE- and iPrGE-etherified dA-AXs showed glass-transition temperatures (Tg) far below their degradation temperatures and gave thermoplastic materials when compression-molded at 140 °C. The BuGE (3 mol)-etherified dA-AX films at 19 and 31% oxidation levels show 244% (±42) and 267% (±72) elongation, respectively. In contrast, iPrGE-dA-AX samples with shorter and branched terminals in the side chains had a maximum of 60% (±19) elongation. No studies have reported such superior elongation of AX thermoplastic films and its relationship with molar substitution and Tg. These findings have implications on the strategic development of chemical modification routes using commercial polymer processing technologies and on fine-tuning structures and properties when specific polysaccharide-based polymers are used to engineer bio-based products for film, packaging, and substrates for stretchable electronic applications.

Composition and structure of cell wall ulvans recovered from Ulva spp. along the Swedish west coast.

The cell wall polysaccharide ulvan was isolated from two species of the seaweed Ulva collected along the Swedish west coast. Acidic extraction was benchmarked against hot water extraction with enzymatic purification and against commercial ulvan. Extracted ulvan contained 11-18 % g/g of ash, some protein (up to 1.3 % g N/g) but minimal colored impurities. The ulvans had high molecular weights (660,000-760,000 g/mol) and were composed of 77-79 % g/g carbohydrates, mainly rhamnose, xylose, glucose, glucuronic acid, and iduronic acid. The extraction protocol and the ulvan source strongly impact the molecular weight and the chemical composition. Acidic extraction caused almost complete desulfation of the isolated ulvan while the other method preserved a significant degree of SO3 substituents. Elemental analysis of ash remaining after thermal degradation showed presence of common mineral elements such as Na, Ca, Mg, Al, and K, but none of the heavy metals Pb, Hg, or As.

Accumulation of FITC near stratum corneum-visualizing epidermal distribution of a strong sensitizer using two-photon microscopy.

BACKGROUND: The allergenic potency of a hapten is related to its skin penetration properties, but little is known about the distribution of haptens in the skin following topical application. OBJECTIVES: The aim of this study was to investigate the diffusion and epidermal distribution using two-photon microscopy (TPM) of two fluorescent compounds. METHODS: Sensitizing capacities of fluorescein isothiocyanate (FITC) and fluorescein were investigated using the local lymph node assay. Chemical reactivity of the compounds was analysed, and their distribution in human epidermis was visualized using TPM and confocal microscopy. Also the in vitro diffusion through epidermis of FITC and fluorescein has been examined. RESULTS: FITC was classified as an extreme sensitizer, whereas fluorescein was non-sensitizing. TPM and confocal microscopy showed an accumulation of FITC in stratum corneum (SC), whereas fluorescein was more evenly distributed in epidermis. The diffusion of fluorescein through epidermis was three times higher than that of FITC. CONCLUSIONS: TPM, which has never been used in this context before, is a promising tool for visualizing the distribution of fluorescent compounds of varying reactivity in intact skin. The strong allergen FITC is mainly retained in or adjacent to SC, whereas most fluorescein diffused through the epidermis.

New features of arabinoxylan ethers revealed by using multivariate analysis.

Hemicelluloses are a relatively unused renewable resource. One reason is their broad structure variety that makes it hard to understand structure-property relations. In this study arbinoxylan, extracted from barley husk, was chemically modified into hydroxypropyl methyl-, hydroxypropyl- and methyl arabinoxylan. The relationship between structure and phase behavior was investigated by using multivariate analysis. The arabinoxylan ethers were characterized using mid-infrared FTIR spectroscopy and from principal components analysis, PCA, structural or physical variations between samples were visualized. With orthogonal projections to latent structures, OPLS, vibrations specific for arabinoxylan hydroxypropyl and methyl substitutions was assigned. Among the observed differences between chemical derivatives was an intensity change in the water vibration. The differences in hydration were related to clouding phase behavior of the arabinoxylan ethers. This study shows that multivariate analysis methods are useful for finding unexpected and/or hidden features in the polysaccharide structure.

The acute and late toxicity results of a randomized phase II dose-escalation trial in non-small cell lung cancer (PET-boost trial).

BACKGROUND AND PURPOSE: The PET-boost randomized phase II trial (NCT01024829) investigated dose-escalation to the entire primary tumour or redistributed to regions of high pre-treatment FDG-uptake in inoperable non-small cell lung cancer (NSCLC) patients. We present a toxicity analysis of the 107 patients randomized in the study. MATERIALS AND METHODS: Patients with stage II-III NSCLC were treated with an isotoxic integrated boost of ≥72 Gy in 24 fractions, with/without chemotherapy and strict dose limits. Toxicity was scored until death according to the CTCAEv3.0. RESULTS: 77 (72%) patients were treated with concurrent chemoradiotherapy. Acute and late ≥G3 occurred in 41% and 25%. For concurrent (C) and sequential or radiotherapy alone (S), the most common acute ≥G3 toxicities were: dysphagia in 14.3% (C) and 3.3% (S), dyspnoea in 2.6% (C) and 6.7% (S), pneumonitis in 0% (C) and 6.7% (S), cardiac toxicity in 6.5% (C) and 3.3% (S). Seventeen patients died of which in 13 patients a possible relation to treatment could not be excluded. In 10 of these 13 patients progressive disease was scored. Fatal pulmonary haemorrhages and oesophageal fistulae were observed in 9 patients. CONCLUSION: Personalized dose-escalation in inoperable NSCLC patients results in higher acute and late toxicity compared to conventional chemoradiotherapy. The toxicity, however, was within the boundaries of the pre-defined stopping rules.

Compounds based on 5-(perylen-3-ylethynyl)uracil scaffold: High activity against tick-borne encephalitis virus and non-specific activity against enterovirus A.

Rigid amphipathic fusion inhibitors (RAFIs) are potent antivirals based on a perylene core linked with a nucleoside moiety. Sugar-free analogues of RAFIs, 5-(perylen-3-ylethynyl)uracil-1-acetic acid 1 and its amides 2, were synthesized using combined protection group strategy. Compounds 1 and 2 appeared to have low toxicity on porcine embryo kidney (PEK) or rhabdomiosarcoma (RD) cells together with remarkable activity against enveloped tick-borne encephalitis virus (TBEV): EC50 values vary from 0.077 µM to subnanomolar range. Surprisingly, 3-pivaloyloxymethyl (Pom) protected precursors 7 and 8 showed even more pronounced activity. All the compounds showed no activity against several non-enveloped enteroviruses, except 4-hydroxybutylamides 2d,g, which inhibited the reproduction of enterovirus A71 with EC50 50-100 µM, with a non-specific mode of action. The results suggest that the carbohydrate moiety of RAFI nucleosides does not play a crucial role in their antiviral action, and biological activity of the 5-(perylen-3-ylethynyl)uracil scaffold can be effectively modulated by substituents in positions 1 and 3. The high antiviral activity of these new compounds, coupled with low toxicity advocate their potential role in antiviral therapy.

Periodate oxidation of xylan-based hemicelluloses and its effect on their thermal properties.

Hemicellulose from pulp mill process water and crop residuals from food production often end up in waste streams or burnt for energy contribution. These waste products contain valuable biopolymers but lack many attributes needed for use in applications such as food and medical or consumer products. This study reports on an investigation of the periodate oxidation of hardwood xylan and arabinoxylan (AX) from wheat bran to produce materials with new functionalities. The study explores how to control the oxidation degree and describes structural differences between the two xylan-based polymers. For the xylan samples, the oxidation resulted in a lowering of the glass transition temperature (Tg), indicating a more flexible chain due to ring-opening of the xylan anhydro-sugar units. For the AX samples, the arabinose side-groups were instead oxidized, hindering oxidation on part of the xylose units, which resulted in a crosslinked network with an unchanged Tg but reduced intrinsic viscosity.

In silico and in vitro studies of the reduction of unsaturated α,ß bonds of trans-2-hexenedioic acid and 6-amino-trans-2-hexenoic acid - Important steps towards biobased production of adipic acid.

The biobased production of adipic acid, a precursor in the production of nylon, is of great interest in order to replace the current petrochemical production route. Glucose-rich lignocellulosic raw materials have high potential to replace the petrochemical raw material. A number of metabolic pathways have been proposed for the microbial conversion of glucose to adipic acid, but achieved yields and titers remain to be improved before industrial applications are feasible. One proposed pathway starts with lysine, an essential metabolite industrially produced from glucose by microorganisms. However, the drawback of this pathway is that several reactions are involved where there is no known efficient enzyme. By changing the order of the enzymatic reactions, we were able to identify an alternative pathway with one unknown enzyme less compared to the original pathway. One of the reactions lacking known enzymes is the reduction of the unsaturated α,ß bond of 6-amino-trans-2-hexenoic acid and trans-2-hexenedioic acid. To identify the necessary enzymes, we selected N-ethylmaleimide reductase from Escherichia coli and Old Yellow Enzyme 1 from Saccharomyces pastorianus. Despite successful in silico docking studies, where both target substrates could fit in the enzyme pockets, and hydrogen bonds with catalytic residues of both enzymes were predicted, no in vitro activity was observed. We hypothesize that the lack of activity is due to a difference in electron withdrawing potential between the naturally reduced aldehyde and the carboxylate groups of our target substrates. Suggestions for protein engineering to induce the reactions are discussed, as well as the advantages and disadvantages of the two metabolic pathways from lysine. We have highlighted bottlenecks associated with the lysine pathways, and proposed ways of addressing them.

A secondary analysis of FDG spatio-temporal consistency in the randomized phase II PET-boost trial in stage II-III NSCLC.

PURPOSE: FDG-PET scans have shown spatial consistency in NSCLC patients before and following chemoradiotherapy, implying radioresistance. We hypothesized that patients, who received FDG-PET redistributed dose painting, would demonstrate reduced spatial consistency when compared to registered patients or to escalated dose treatment. METHODS: Stage II-IIIB, inoperable NSCLC patients were randomized in a phase II trial (NCT01024829) to (chemo)radiotherapy of either homogeneous boosting to the primary tumor, or redistributed inhomogeneous boosting to the GTV subvolume (FDG-SUV > 50% SUVmax). Patients who could not be boosted (≥72 Gy) received 66 Gy in 24 fractions. Spatial consistency of pre-treatment and post-treatment (3 months) FDG-PET scans was measured by various overlap fraction thresholds. RESULTS: 66/82 patients analyzed received randomized treatment in the trial. Thresholds of 50% SUVmax pre-treatment and 70% SUVmax post-treatment yielded a median overlap fraction of 0.63 [interquartile range: 0.15-0.93], with similar results for other thresholds. No significant differences were found among overlap fractions of the treatment groups. A high incidence of FDG-uptake in normal lung (grade-1 pneumonitis: 73%) was found post-treatment. CONCLUSION: FDG redistributed boosting did not reduce FDG spatial consistency from pre-treatment to post-treatment, which was highly variable among patients. The study found high numbers of patients with lung inflammation after treatment.