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Lignin can affect the enzymatic hydrolysis efficiency of lignocellulose. In this study, the lignin isolated from sugarcane bagasse (SCB) pretreated with p-toluenesulfonic acid (PL) was firstly aminated, and then the effects of PL and aminated PL (APL) on the bagasse enzymatic hydrolysis efficiency (EHE) were investigated. The results showed that the addition of PL and APL promoted the EHE, and EHE with APL (73.82 %) was higher than PL (51.39 %). To explore the reason, the data were further analyzed including cellulase adsorption capacity, enzyme activity, cellulase-lignin interaction, and molecular docking. It was found that APL adsorbed more cellulase (27.83 mg protein/g lignin) than PL (4.96 mg protein/g lignin), resulting from the greater interaction force and lower binding free energy between APL and cellulase. The addition of APL more remarkably enhanced the cellobiohydrolase and endoglucanase activities than PL due to more effectively inducing cellulase conformation optimization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hydrogen sulfide (H 2 S) is a ubiquitous gaseous signaling molecule that has an important role in many physiological and pathological processes in mammalian tissues, with the same importance as two others endogenous gasotransmitters such as NO (nitric oxide) and CO (carbon monoxide). Endogenous H 2 S is involved in a broad gamut of processes in mammalian tissues including inflammation, vascular tone, hypertension, gastric mucosal integrity, neuromodulation, and defense mechanisms against viral infections as well as SARS-CoV-2 infection. These results suggest that the modulation of H 2 S levels has a potential therapeutic value. Consequently, synthetic H 2 S-releasing agents represent not only important research tools, but also potent therapeutic agents. This review has been designed in order to summarize the currently available H 2 S donors; furthermore, herein we discuss their preparation, the H 2 S-releasing mechanisms, and their -biological applications.

Environmental pollution is one of the most important problems that human beings face. Today, nanotechnology has played an important role in green chemistry and the use of nanoparticles in the removal of environmental pollutants is one of the newest methods of removing pollutants in the world. So, in this study, Nickel oxide nanoparticles (NiO NPs) of this work were successfully synthesized via a green method by the usage of nickel nitrate hexahydrate as the source of metal and Biebersteinia multifida extract as the stabilizing agent throughout different annealing temperatures. The physicochemical properties of the obtained NiO NPs were characterized through the application of scanning electron microscopy (SEM), energy dispersive X-ray (EDX), powder X-ray diffraction (PXRD), ultraviolet visible (UV-vis), and Raman analysis. According to the results of SEM and PXRD, the prepared product contained a satisfying distribution and very fine cubic structure with minimal accumulation. The average crystal size of prepared nanoparticles was obtained 54-58 nm. The energy band gap of synthesized NiO NPs was calculated 3-3.7 using Tauc equation. The photocatalytic performance of NiO NPs was investigated under visible light through the decolourization reaction of acid orange 7 (AO7) dye in aqueous solution. Being composed at 300 °C of annealing temperature, these nanoparticles exhibited excellent adsorption and photocatalytic activity (90.2%) toward AO7 dye. Therefore, it can be indicated that the synthesized NiO NPs demonstrated an excellent dispersion in dye solution, as well as considerable photocatalytic activity., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Zero-valent iron (ZVI) pre-treatment in sequential strategy for removal of non-biodegradable azo-dye Orange II by activated-sludge was quantitatively examined. The decolorization and TOC (total organic carbon) removal of Orange II by ZVI pre-treatment were examined in the ranges of pH from 3 to 11 and ZVI dosage from 500 to 2000 mgL -1 . While the decolorization was enhanced with decreasing pH and the optimal pH for decolorization was found at pH 3, the TOC removal rate at pH 3 remained at 22.2% and the maximum TOC removal rate of 78.2% was obtained at pH 4. The decolorization and TOC removal of Orange II were monotonously increased with increasing ZVI dosage. To quantify the ZVI pre-treatment, the contributions of redox degradation, complexation/precipitation and adsorption to TOC removal by ZVI were defined. Novel kinetic models for the ZVI pre-treatment and activated-sludge post-treatment were developed. The proposed kinetic models satisfactorily predicted the transitional behaviors of the ZVI pre-treatment and activated-sludge post-treatment and the contributions of redox degradation, complexation/precipitation and adsorption to TOC removal by the ZVI pre-treatment. The complete removal of non-biodegradable azo-dye Orange II of 300 mgL -1 was accomplished by 78.2% removal after 360 min ZVI pre-treatment with the ZVI dosage of 1000 mgL -1 at pH 4 and subsequently 21.8% removal after 480 min activated-sludge post-treatment. The ZVI pre-treatment integrated with activated-sludge post-treatment was proved to be an effective strategy for treating non-biodegradable pollutants., Competing Interests: Declaration of competing interest Authors have a responsibility to disclose interests that might appear to affect their ability to present data objectively. These include relevant financial, personal, political, intellectual, or religious interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Head and neck connective tissue lesions may have diverse calcifications within the fibrous connective tissue stroma. The perplexity involved in the identification and determination of the nature or degree of calcification through routine hematoxylin and eosin (H&E) stains necessitates the usage of a specific, simple, and cost- and time-effective differential staining techniques. The aim of the present study was to develop criteria to distinguish bone formation from bone resorption using methylene blue-acid fuchsin (MB/AF) stain and the role of collagen fibers in the identification of stromal calcifications using polarizing microscopy with picrosirius red stain. Twenty cases with pathological diagnoses for various stromal calcifications in maxillofacial lesions were retrieved from the departmental archives. Decalcified formalin fixed paraffin embedded tissue sections were stained with hematoxylin and eosin, Masson's trichrome (MT), methylene blue-acid fuchsin (MB/AF), and picrosirius red. The stained sections were assessed to identify the calcifications found in the surrounding connective tissue stroma. It was observed that most cases showed maximum staining intensity with MB/AF stain as compared to the other staining methods. Moreover, the results suggested that contrast between calcification and stromal soft tissue was best distinguished with the MB/AF stain except in the case of dystrophic calcifications. Along with this, polarizing microscopy with picrosirius red enables better characterization of stromal components. Although the H&E stain and a connective tissue stain i.e. Masson's trichrome, are employed routinely in histopathology; the use of special stains such as MB-AF and picrosirius red facilitates the identification of calcifications from the stromal tissues.

Gankyrin is an oncoprotein overexpressed in numerous cancer types and appears to play a key role in regulating cell proliferation, cell growth, and cell migration. These roles are largely due to gankyrin's protein-protein interaction with the 26S proteasome. We previously published a study exploring the aryl sulfonate ester of cjoc42 in an effort to enhance gankyrin binding and inhibit cancer cell proliferation. In order to further improve the gankyrin binding ability of the cjoc42 scaffold, an extensive SAR for the aryl-triazole moiety of cjoc42 was developed. Our cjoc42 derivatives exhibited enhanced gankyrin binding, as well as enhanced antiproliferative activity against Hep3B, HepG2, A549, and MDA-MB-231 cancer cell lines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rationale: Following an ever-increased focus on personalized medicine, there is a continuing need to develop preclinical molecular imaging modalities to guide the development and optimization of targeted therapies. Near-Infrared (NIR) Macroscopic Fluorescence Lifetime Förster Resonance Energy Transfer (MFLI-FRET) imaging offers a unique method to robustly quantify receptor-ligand engagement in live intact animals, which is critical to assess the delivery efficacy of therapeutics. However, to date, non-invasive imaging approaches that can simultaneously measure cellular drug delivery efficacy and metabolic response are lacking. A major challenge for the implementation of concurrent optical and MFLI-FRET in vivo whole-body preclinical imaging is the spectral crowding and cross-contamination between fluorescent probes. Methods: We report on a strategy that relies on a dark quencher enabling simultaneous assessment of receptor-ligand engagement and tumor metabolism in intact live mice. Several optical imaging approaches, such as in vitro NIR FLI microscopy (FLIM) and in vivo wide-field MFLI, were used to validate a novel donor-dark quencher FRET pair. IRDye 800CW 2-deoxyglucose (2-DG) imaging was multiplexed with MFLI-FRET of NIR-labeled transferrin FRET pair (Tf-AF700/Tf-QC-1) to monitor tumor metabolism and probe uptake in breast tumor xenografts in intact live nude mice. Immunohistochemistry was used to validate in vivo imaging results. Results: First, we establish that IRDye QC-1 (QC-1) is an effective NIR dark acceptor for the FRET-induced quenching of donor Alexa Fluor 700 (AF700). Second, we report on simultaneous in vivo imaging of the metabolic probe 2-DG and MFLI-FRET imaging of Tf-AF700/Tf-QC-1 uptake in tumors. Such multiplexed imaging revealed an inverse relationship between 2-DG uptake and Tf intracellular delivery, suggesting that 2-DG signal may predict the efficacy of intracellular targeted delivery. Conclusions: Overall, our methodology enables for the first time simultaneous non-invasive monitoring of intracellular drug delivery and metabolic response in preclinical studies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: The efficacy of antibody-based therapeutics depends on successful drug delivery into solid tumors; therefore, there is a clinical need to measure intratumoral antibody distribution. This study aims to develop and validate an imaging and computation platform to directly quantify and predict antibody delivery into human head and neck cancers in a clinical study., Experimental Design: Twenty-four patients received systemic infusion of a near-infrared fluorescence-labeled therapeutic antibody followed by surgical tumor resection. A computational platform was developed to quantify the extent of heterogeneity of intratumoral antibody distribution. Both univariate and multivariate regression analyses were used to select the most predictive tumor biological factors for antibody delivery. Quantitative image features from the pretreatment MRI were extracted and correlated with fluorescence imaging of antibody delivery., Results: This study not only confirmed heterogeneous intratumoral antibody distribution in-line with many preclinical reports, but also quantified the extent of interpatient, intertumor, and intratumor heterogeneity of antibody delivery. This study demonstrated the strong predictive value of tumor size for intratumoral antibody accumulation and its significant impact on antibody distribution in both primary tumor and lymph node metastasis. Furthermore, this study established the feasibility of using contrast-enhanced MRI to predict antibody delivery., Conclusions: This study provides a clinically translatable platform to measure antibody delivery into solid tumors and yields valuable insight into clinically relevant antibody tumor penetration, with implications in the selection of patients amenable to antibody therapy and the design of more effective dosing strategies., (©2020 American Association for Cancer Research.)

A combined stimulus-responsive photosensitiser and drug release system based on mesoporous silica nanoparticles was prepared. This nanoplatform encapsulated molecules of zinc(ii) phthalocyanine substituted with a glutathione-cleavable 2,4-dinitrobenzenesulfonate quencher and doxorubicin linked via a singlet-oxygen-cleavable 9,10-dialkoxyanthracene linker. In the presence of glutathione (in mM range) and upon irradiation (λ > 610 nm), the phthalocyanine units were activated by detaching from the quenching component to emit fluorescence and generate singlet oxygen. The latter subsequently cleaved the 9,10-dialkoxyanthracene linker to trigger the release of a doxorubicin derivative. The glutathione- and light-controlled activation and drug-release processes on this nanoplatform were demonstrated in phosphate buffered saline. The activation in fluorescence emission by intracellular thiols was also shown inside HepG2 human hepatocellular carcinoma cells. Upon irradiation, the nanosystem exhibited high cytotoxicity due to the photodynamic effect of the activated phthalocyanine units, but the cytotoxic effect of the released Dox moieties was not notable probably due to their reduced cytotoxicity as a result of the pendant substituent and the low drug loading in the nanoparticles.

Cancer cells use elevated glutathione (GSH) levels as an inner line of defense to evade apoptosis and develop drug resistance. In this study, we describe a novel 2,4-nitrobenzenesulfonyl (DNS) protected 2-hydroxyisophthalamide system that exploits GSH for its activation into free 2-hydroxyisophthalamide forming supramolecular M + /Cl - channels. Better permeation of the DNS protected compound into MCF-7 cells compared to the free 2-hydroxyisophthalamide and GSH-activatable ion transport resulted in higher cytotoxicity, which was associated with increased oxidative stress that further reduced the intracellular GSH levels and altered mitochondrial membrane permeability leading to the induction of the intrinsic apoptosis pathway. The GSH-activatable transport-mediated cell death was further validated in rat insulinoma cells (INS-1E); wherein the intracellular GSH levels showed a direct correlation to the resulting cytotoxicity. Lastly, the active compound was found to restrict the growth and proliferation of 3D spheroids of MCF-7 cells with efficiency similar to that of the anticancer drug doxorubicin., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An efficient MnCeO x composite was successfully synthesized for activation of persulfate to degrade acid orange 7 (AO7) and ofloxacin. Pollutants degradation efficiencies with different catalytic systems were investigated. Results showed the performance of MnCeO x was better than MnO x, CeO 2 and MnO x  + CeO 2 . Thus, there was a clear synergistic effect (Se) between Mn and Ce in the composite, and the Se was 73.8% for AO7 and 39.6% for ofloxacin. In addition, AO7 removal fitted 1st order reaction while ofloxacin removal fitted 2nd order reaction in MnCeO x /persulfate system. Moreover, MnCeO x /persulfate system showed high efficiency in pH range of 5-9. Mechanism analysis showed that SO 4 - and OH on the surface of the catalyst were the main active species, and O 2 - also played an important role in pollutants degradation. Furthermore, MnCeO x showed high activity in actual water. Finally, the possible degradation pathway of ofloxacin was proposed according to the high performance liquid chromatography-mass spectrometry result. Overall, this study provides an efficient and stable catalyst to activate persulfate to degrade refractory pollutants., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Understanding the electrode configuration is vital for the successful application of bioelectrochemical system (BES) in recalcitrant wastewater treatment. Especially in those traditional anaerobic processes that integrate with BES to construct effective hybrid bioreactors. Hybrid bioreactors employed granular graphite as electrode material achieved 86.62 ± 1.83% decolorization efficiency of azo dye acid orange 7 (AO7) at influent AO7 loading rate of 800 g/(m 3 ∙d) and it was about 6% higher than that with carbon fiber brush electrodes. Such electrodes were positioned above the anaerobic sludge layer and higher efficiency (8%) than the reactors with electrodes placed beneath the sludge layer was observed. Tracer experiments and modeling of residence time distribution indicated that the fluid pattern in hybrid bioreactors was modified to plug flow pattern and had a better consummate mixing ability compared to the conventional anaerobic reactor. Simulation using computational fluid dynamics technique showcased favorable mass transfer near electrode modules. The hydrodynamics of simulation and experimental results were connected by simplifying electrode module as a porous media model. This study thus proved that hybrid bioreactors can effectively enhance wastewater treatment comprehensively through the analysis of decolorization performance and hydrodynamics., (Copyright © 2019. Published by Elsevier B.V.)

The physiological constraints on bud burst in woody perennials, including vascular development and oxygenation, remain unresolved. Both light and tissue oxygen status have emerged as important cues for vascular development in other systems; however, grapevine buds have only a facultative light requirement, and data on the tissue oxygen status have been confounded by the spatial variability within the bud. Here, we analysed apoplastic development at early stages of grapevine bud burst and combined molecular modelling with histochemical techniques to determine the pore size of cell walls in grapevine buds. The data demonstrate that quiescent grapevine buds were impermeable to apoplastic dyes (acid fuchsin and eosin Y) until after bud burst was established. The molecular exclusion size was calculated to be 2.1 nm, which would exclude most macromolecules except simple sugars and phytohormones until after bud burst. We used micro-computed tomography to demonstrate that tissue oxygen partial pressure data correlated well with structural heterogeneity of the bud and differences in tissue density, confirming that the primary bud complex becomes rapidly and preferentially oxygenated during bud burst. Taken together, our results reveal that the apoplastic porosity is highly regulated during the early stages of bud burst, suggesting a role for vascular development in the initial, rapid oxygenation of the primary bud complex., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Purpose: Prostate carcinoma consists of tumor epithelium and malignant stroma. Until recently, diagnostic and therapeutic efforts have focused exclusively on targeting characteristics of the tumor epithelium, ignoring opportunities to target inflammatory infiltrate and extracellular matrix components. Prostate tumors are rich in tumor-associated macrophages (TAMs), which can be either of the cytotoxic M1 or protumorigenic M2 phenotype. We have quantified the proportion of each in seven common human prostate tumor lines grown subcutaneously in athymic nude mice and have imaged macrophage densities in vivo in xenografts derived from these lines., Procedures: A panel of seven human prostate cancer xenografts was generated in intact male athymic nude mice reflecting variable expression of the androgen receptor (AR) and prostate-specific membrane antigen (PSMA). Mice were imaged ex vivo using near-infrared fluorescence (NIRF) imaging for PSMA expression and total macrophage densities to enable direct comparison between the two. Tumors were harvested for sectioning and additional staining to delineate M1 and M2 phenotype along with vascular density., Results: Macrophage polarization analysis of sections revealed that all xenografts were > 94% M2 phenotype, and the few M1-polarized macrophages present were confined to the periphery. Xenografts displaying the fastest growth were associated with the highest densities of macrophages while the slowest growing tumors were characterized by focal, tumor-infiltrating macrophage densities. Xenograft sections displayed a strong positive spatial relationship between macrophages, vasculature, and PSMA expression., Conclusions: Prostate TAM disposition can be imaged ex vivo and is associated with growth characteristics of a variety of tumor subtypes regardless of PSMA or AR expression.

The application of membrane and cell wall selective fluorescent dyes for live-cell imaging analyses of organelle dynamics in fungal cells started two decades ago and since then continues to contribute greatly to our understanding of the filamentous fungal lifestyle. This paper provides a practical guide for the utilization of the two membrane dyes FM 1-43 and FM 4-64 and the four cell wall stains Calcofluor White M2R, Solophenyl Flavine 7GFE 500, Pontamine Fast Scarlet 48 and Congo Red. The focus is on their low-dose application to ascertain artefact-free staining, their co-imaging properties, and their quantitative evaluation. The presented methods are applicable to all filamentous fungal samples that can be prepared in the described ways. The fundamental staining approaches can serve as starting points for adaptations to species that might require different cultivation conditions. First, biophysical and biochemical properties are reviewed as their understanding is essential for using these dyes as truly vital fluorescent stains. Secondly, step-by-step protocols are presented that detail the preparation of various fungal sample types for fluorescent live-cell imaging. Finally, example experiments illustrate different approaches to: (1) identify defects in the spatio-temporal organization of endocytosis in genetic mutants, (2) comparatively characterize shared and distinct co-localization of GFP-labeled target proteins in the endocytic pathway, (3) identify morphogenetic cell wall defects in a genetic mutant, and (4) monitor cell wall biogenesis in real time.

Introducing peroxymonosulfate (PMS) and peroxydisulfate (PDS) into the photocatalytic fuel cell (PFC) system were investigated by comparing the Reactive Brilliant Blue (KN-R) degradation and synchronous electricity production. The two persulfates (PS) themselves are strong oxidant, and could be activated and as electron sacrificial agent in the PFCs, facilitating the photoelectrocatalysis and expanding redox to the entire cell space. Hence, the two established PFC/PS systems manifested prominent cell performances, enhancing the KN-R decomposition and electric power production relative to the virgin PFC. Thereinto, the KN-R removal rate of PFC/PMS was faster than that of PFC/PDS, but an opposite trend appeared in the electricity generation. Besides, the cell performances of the two cooperative systems were evaluated at different operation conditions, including PS dosage, solution pH, and irradiation strength. Moreover, the dye elimination principle was explored by radicals scavenging experiment, and the consequence revealed that hydroxyl radical (HO • ), sulfate radical (SO 4 • -) and singlet oxygen were chief active species in the PFC/PMS, and HO • , SO 4 • - and superoxide anion played the key roles in the PFC/PDS. Furthermore, the calculated economic indicator demonstrated that the economy of the two synergistic processes were greater than that of UV/PS and solo PFC, and the PFC/PDS was more cost-effective than PFC/PMS., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Although a large amount of textile wastewater is discharged at high temperatures, azo dye reduction under extreme-thermophilic conditions by mixed cultures has gained little attention. In this study, Acid Orange 7 (AO7) was used as the model azo dye to demonstrate the decolorization ability of an extreme-thermophilic mixed culture. The results showed that a decolorization efficiency of over 90% was achieved for AO7. The neutral red (NR, 0.1 mM) could promote AO7 decolorization, in which the group of Cell + NR offered the highest decolorization rate of 1.568 1/h and t 1/2 was only 0.44 h, whereas after CuCl 2 addition, the decolorization rate (0.141 1/h) was lower and t 1/2 (4.92 h) was much longer. Thus, CuCl 2 notably inhibited this process. Caldanaerobacter (64.0%) and Pseudomonas (25.4%) were the main enriched bacteria, which were not reported to have the ability for dye decolorization. Therefore, this study extends the application of extreme-thermophilic biotechnology., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Azo dyes are recalcitrant pollutants, which are toxic, carcinogenic, mutagenic and teratogenic, that constitute a significant burden to the environment. The decolorization and the mineralization efficiency of Remazol Brillant Orange 3R (RBO 3R) was studied using a probiotic consortium ( Lactobacillus acidophilus and Lactobacillus plantarum ). Biodegradation of RBO 3R (750 ppm) was investigated under shaking condition in Mineral Salt Medium (MSM) solution at pH 11.5 and temperature 25°C. The bio-decolorization process was further confirmed by FTIR and UV-Vis analysis. Under optimal conditions, the bacterial consortium was able to decolorize the dye completely (>99%) within 12 h. The color removal was 99.37% at 750 ppm. Muliplex PCR technique was used to detect the Lactobacillus genes . Using phytotoxicity, cytotoxicity, mutagenicity and biototoxicity endpoints, toxicological studies of RBO 3R before and after biodegradation were examined. A toxicity assay signaled that biodegradation led to detoxification of RBO 3R dye.

Autism is a complex neurodevelopmental disorder with a high incidence rate. It is characterized by deficits in communication, a lack of social skills, cognitive inflexibility, and stereotypical behaviors. Autism has been gradually increasing in children over the past several years, without the existence of an effective treatment. BTBR T + Itpr3 tf /J (BTBR) mice serve as an accepted model to evaluate autistic-like behaviors as they display core behavioral symptoms displayed in autism. Previous findings showed that S3I-201, a selective Stat3 inhibitor, can be used to treat neuroinflammation disorders. Previously, we showed that S3I-201 treatment has therapeutic effects on autism-like behaviors, and Th1/Th17 and regulatory T cells in BTBR mice. The objective of the present study was to further explore the role of S3I-201 in BTBR mice, and this was performed by investigating the effects of S3I-201 treatment on lymphocyte activation markers (CD4 + CD25 + and CD4 + CD69 + ), chemokine receptors (CD4 + CCR6 + , CD4 + CCR7 + , CD4 + CXCR4 + , and CD4 + CXCR5 + ), and proinflammatory cytokines (CD4 + IL-6 + and CD4 + TNF-α + ) in the spleen cells of BTBR and C57BL/6 (C57) mice. The mRNA and protein expression levels of CD69, CCR6, CCR7, CXCR4, CXCR5, IL-1β, IL-6, and TNF-α were examined in the brain tissues, and in BTBR mice, a significant decrease in CD25, CD69, CCR6, CCR7, CXCR4, CXCR5, IL-6, and TNF-α producing CD4 + T cells was observed. The present findings suggest that treatment with S3I-201 may be a therapeutic approach to improve immune abnormalities in a subgroup of autistic subjects., (Copyright © 2019. Published by Elsevier Inc.)

Although the three-dimensional structures of mouse and Torpedo californica acetylcholinesterase are very similar, their responses to the covalent sulfonylating agents benzenesulfonyl fluoride and phenylmethylsulfonyl fluoride are qualitatively different. Both agents inhibit the mouse enzyme effectively by covalent modification of its active-site serine. In contrast, whereas the Torpedo enzyme is effectively inhibited by benzenesulfonyl fluoride, it is almost completely resistant to phenylmethylsulfonyl fluoride. A bottleneck midway down the active-site gorge in both enzymes restricts access of ligands to the active site at the bottom of the gorge. Molecular dynamics simulations revealed that the mouse enzyme is substantially more flexible than the Torpedo enzyme, suggesting that enhanced 'breathing motions' of the mouse enzyme relative to the Torpedo enzyme may explain why phenylmethylsulfonyl fluoride can reach the active site in mouse acetylcholinesterase, but not in the Torpedo enzyme. Accordingly, we performed docking of the two sulfonylating agents to the two enzymes, followed by molecular dynamics simulations. Whereas benzenesulfonyl fluoride closely approaches the active-site serine in both mouse and Torpedo acetylcholinesterase in such simulations, phenylmethylsulfonyl fluoride is able to approach the active-site serine of mouse acetylcholinesterase, but remains trapped above the bottleneck in the Torpedo enzyme. Our studies demonstrate that reliance on docking tools in drug design can produce misleading information. Docking studies should, therefore, also be complemented by molecular dynamics simulations in selection of lead compounds. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:CHEMBIOINT:2., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To identify the enzymes potentially useful for the decolorization of azo dyes, the secretome of the ascomycetous fungus Myrothecium roridum IM6482 was studied by using a bottom-up proteomic approach. Among the identified proteins, the most promising for dye removal was laccase, which decolorized respectively, 66, 91, 79, and 80% of Acid Blue 113 (AB 113), Acid Red 27 (AR 27), Direct Blue 14 (DB 14), and Acid Orange 7 (AO 7). The degradation of dyes was enhanced at the wide range of pH from 4 to 8. The addition of redox mediators allowed eliminating AB 113 in concentrations up to 400 mg/L and decolorization of the simulated textile effluent. Microbial toxicity and phytotoxicity tests indicated that dyes are converted into low-toxicity metabolites. This is the first insight into the M. roridum secretome, its identification and its application for removal of select azo dyes. Obtained results extended knowledge concerning biodegradative potential of ascomycetous, ligninolytic fungi and will contribute to the improvement of dye removal by fungi.

A zinc(II) phthalocyanine substituted with three 2,4-dinitrobenzenesulfonate (DNBS) groups and a cyclic arginine-glycine-aspartic acid (cRGDfK) moiety was prepared and characterized. With three strongly electron-withdrawing DNBS groups, this compound was fully quenched in terms of fluorescence emission and singlet oxygen generation in N,N-dimethylformamide and phosphate buffered saline due to the strong photoinduced electron transfer effect. In the presence of glutathione (GSH), which is the most abundant intracellular thiol particularly in tumor cells, the DNBS moieties were cleaved, thereby restoring these photoactivities and making the conjugate as a GSH-activated photosensitizer. Being a well-known integrin antagonist, the cyclic RGD peptide sequence could enhance the localization of the conjugate in integrin-upregulated tumor cells. As shown by confocal laser scanning microscopy and flow cytometry, the intracellular fluorescence intensity of the conjugate was significantly higher in the integrin-positive A549 and MDA-MB-231 cells than in the integrin-negative MCF-7 and HEK293 cells. The photocytotoxicity of the conjugate against MDA-MB-231 cells was also higher than that toward MCF-7 cells. The results suggest that this dual-functional photosensitizer is a promising candidate for targeted photodynamic therapy., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The plasmonic cerium vanadate (CeVO 4 ) semiconductor and plasmonic silver (Ag) metal exhibit a localized surface plasmon resonance (LSPR) effect in the visible (Vis)-light region; however, weak absorption in the near-infrared (NIR) region restricts their environmental remediation and biomedical application. Herein, CeVO 4 /Ag nanohybrids with self-assembled heterostructure and improved Vis/NIR light absorption were synthesized from CeVO 4 nanosheets and AgNO 3 solution, which could serve as potential solar-driven catalytic agents and near-infrared (NIR) light responsive anticancer agents. Oleic acid-stabilized CeVO 4 nanosheets were modified with the HS-PEG 1000 -OH by the thiol-ene click reaction and presented self-assembly morphology in aqueous solution due to hydrophobic-hydrophobic interactions. Sulfhydryl (-SH) groups provided stable sites for Ag + ions on the surface of CeVO 4 , and Ag + ions could be directly reduced by Ce 3+ ions to form CeVO 4 /Ag heterojunction nanocrystals (NCs). Due to the higher absorption in the Vis/NIR light region than CeVO 4 nanosheets, CeVO 4 /Ag NCs led to the improved solar light responsive photocatalytic degradation of organic dyes. Upon the exposure of these NCs to an 808 nm laser, CeVO 4 /Ag NCs show high photothermal conversion efficiency, ROS generation ability and photoacoustic (PA) signal for implementing PA imaging-guided photothermal/photodynamic synergistic cancer therapy with better tumor inhibition effect.

The decolourization and detoxification of azo dyes (Orange 2, Acid Orange 6) by fungal laccase from Trametes versicolor were evaluated. For laccase catalysed reaction, the azonaphthol Orange 2, with 72.8% decolourization, was degraded more rapidly than the azobenzene Acid Orange 6, with 45.3%. The presence of hydroxyl group at o-position to azo bond in the structure of Orange 2 was more preferable than the presence of two hydroxyl groups at o- and p-positions to azo bond in Acid Orange 6. Although the laccase treatment was more effective for the Orange 2 decolourization, the toxicity of both monoazo dye solutions became less toxic for the prokaryote growth. The phytotoxicity of Orange 2 and Acid Orange 6 solutions after laccase treatment was decreased in the range of 41.2-64.3 %. Also, the photoxicity, as measured by the production of chlorophylls a and b by Chlorella vulgaris and Microcystis aeruginosa, was decreased by laccase treatment of selected monoazo dyes. Our results show that different dyes can be decolorized and detoxified by laccase from T. versicolor in a single step., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Carbon-based catalysts have attracted high attention since they are greener and cheaper, while magnetic nanomaterials are very useful in environmental application because of the easy recovery and operation given by the magnetic separability. Therefore, graphitic carbon nitride modified magnetic carbon nanocomposites Fe 3 O 4 @C/g-C 3 N 4 was prepared herein for the first time as a new carbon-based catalyst for the activation of peroxymonosulfate (PMS). The catalytic properties of Fe 3 O 4 @C/g-C 3 N 4 in activating PMS for the degradation of Acid Orange 7 (AO 7), a model organic pollutant, were investigated. AO 7 degradation efficiency was significantly enhanced after modification of Fe 3 O 4 @C with g-C 3 N 4 , and the composite Fe 3 O 4 @C/g-C 3 N 4 from loading of 5 wt% g-C 3 N 4 and calcined at 300 °C for 30 min exhibited the best performance. AO 7 could be efficiently decolorized using the "Fe 3 O 4 @C/C 3 N 4 (5%) + PSM" system within the pH range of 2-6, and 97% of AO 7 could be removed in 20 min without pH adjustment (pH = 4). Radical quenching and EPR studies confirmed that both sulfate and hydroxyl radicals produced from PMS activation were the active species responsible for the oxidation of AO 7. The degradation mechanism was suggested based on the experimental results and XPS analyses. It was proposed that the CO groups on the carbon surface of Fe 3 O 4 @C rather than the CO in g-C 3 N 4 played a key role as the active sites for PMS activation. The catalyst was magnetically separable and displayed good stability and reusability, thus providing a potentially green catalyst for sustainable remediation of organic pollutants., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Significantly reduced photon scattering and minimal tissue autofluorescence levels in the second biological transparency window (NIR-II; 1000-1700 nm) facilitate higher resolution in vivo biological imaging compared to tradition NIR fluorophores (~700-900 nm). However, the existing palette of NIR-II fluorescent agents including semiconducting inorganic nanomaterials and recently introduced small-molecule organic dyes face significant technical and regulatory hurdles prior to clinical translation. Fortunately, recent spectroscopic characterization of NIR-I dyes (e.g., indocyanine green (ICG), IRDye800CW and IR-12N3) revealed long non-negligible emission tails reaching past 1500 nm. Repurposing the most widely used NIR dye in medicine, in addition to those in the midst of clinical trials creates an accelerated pathway for NIR-II clinical translation. This review focuses on the significant advantage of imaging past 1000 nm with NIR-I fluorophores from both a basic and clinical viewpoint. We further discuss optimizing NIR-I dyes around their NIR-II/shortwave infrared (SWIR) emission, NIR-II emission tail characteristics and prospects of NIR-II imaging with clinically available and commercially available dyes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

In order to provide useful information for the rational design of effective Fenton-like catalyst, a series of Cu-based bimetallic oxides were synthesized and their Fenton-like performances for the degradation of Orange II and ciprofloxacin were compared. The structure, chemical oxidation state, surface charge property and redox ability of the catalysts were also investigated by different characterization techniques. Among them, NiCu exhibited the highest adsorption capacity towards Orange II and the highest activity for the production of OH from H 2 O 2 decomposition, which could be attributed to its high surface area and highly positively charged surface. However, FeCu exhibited the highest activity for the degradation of Orange II. The reason might be that FeCu has more unpaired electrons and higher redox ability, thus promoting the activation of adsorbed Orange II through the electron transfer process. By contrast, NiCu exhibited the highest activity for the removal of ciprofloxacin because ciprofloxacin was mainly degraded by OH. Finally, the main degradation intermediates of Orange II and ciprofloxacin were determined by liquid chromatography-mass spectrometry., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Here, we describe a simple, non-time consuming and inexpensive method for monitoring of Calcofluor white M2R-binding exopolysaccharides in individual bacterial cells. This method was demonstrated by time-lapse microscopy of succinoglycan-producing cells of the plant-symbiotic alpha-proteobacterium Sinorhizobium meliloti. The method is most likely applicable to other bacteria producing β-(1→3) and β-(1→4) linked polysaccharides., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Microbes have potential to convert non-toxic azo dyes into hazardous products in the environment. However, the role of microbes in biotransforming such presumably non-toxic dyes has not been given proper attention, thereby, questions the environmental safety of such compounds. The present study assessed salinity driven microbial degradation of an unregulated azo dye, Acid orange 7 (AO7), under moderately halophilic conditions of textile effluent. The halophilic microbial consortium from effluent decolorized ~97% AO7 (50-500mgL -1 ). The consortium efficiently decolorized the dye at different pH (5-8) and salinity (5-18% NaCl). The 16S rRNA sequence analyses confirmed the presence of Halomonas and Escherichia in the consortium. The FTIR and GC-MS analyses suggested microbial consortium degrade AO7 following symmetric and asymmetric cleavage and yield carcinogenic/mutagenic aromatic byproducts viz. aniline, 1-amino-2-naphthol, naphthalene, and phenyldiazene. In contrast to AO7, the biodegraded products caused molecular, cellular and organism level toxicity. The degraded products significantly reduced: radicle length in root elongation assay; shoot length/biomass in plant growth assays; and caused chromosomal abnormalities and reduced mitotic index in Allium cepa bioassay. We demonstrated that under saline conditions of textile effluent, halophilic microbes convert a presumably non-toxic azo dye into hazardous products. The study calls to review the current toxicity classification of azo dyes and develop environmentally sound regulatory policies by incorporating the role of environmental factors in governing dye toxicity, for environmental safety., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This study investigated the biodegradation performance and characteristics of Sudan I and Acid Orange 7 (AO7) to improve the biological dye removal efficiency in wastewater and optimize the treatment process. The dyes with different water-solubility and similar molecular structure were biologically treated under aerobic condition in parallel continuous-flow mixed stirred reactors. The biophase analysis using microscopic examination suggested that the removal process of the two azo dyes is different. Removal of Sudan I was through biosorption, since it easily assembled and adsorbed on the surface of zoogloea due to its insolubility, while AO7 was biodegraded incompletely and bioconverted, the AO7 molecule was decomposed to benzene series and inorganic ions, since it could reach the interior area of zoogloea due to the low oxidation-reduction potential conditions and corresponding anaerobic microorganisms. The transformation of NH₃-N, SO₄ 2- together with the presence of tryptophan-like components confirm that AO7 can be decomposed to non-toxic products in an aerobic bioreactor. This study provides a theoretical basis for the use of biosorption or biodegradation mechanisms for the treatment of different azo dyes in wastewater., Competing Interests: The authors declare no conflict of interest.

Dyes containing one or more azo linkages are widely applied in cosmetics, tattooing, food and drinks, pharmaceuticals, printing inks, plastics, leather, as well as paper industries. Previously we reported that bacteria living on human skin have the ability to reduce some azo dyes to aromatic amines, which raises potential safety concerns regarding human dermal exposure to azo dyes such as those in tattoo ink and cosmetic colorant formulations. To comprehensively investigate azo dye-induced toxicity by skin bacteria activation, it is very critical to understand the mechanism of metabolism of the azo dyes at the systems biology level. In this study, an LC/MS-based metabolomics approach was employed to globally investigate metabolism of azo dyes by Staphylococcus aureus as well as their effects on the metabolome of the bacterium. Growth of S. aureus in the presence of Sudan III or Orange II was not affected during the incubation period. Metabolomics results showed that Sudan III was metabolized to 4-(phenyldiazenyl) aniline (48%), 1-[(4-aminophenyl) diazenyl]-2-naphthol (4%) and eicosenoic acid Sudan III (0.9%). These findings indicated that the azo bond close to naphthalene group of Sudan III was preferentially cleaved compared with the other azo bond. The metabolite from Orange II was identified as 4-aminobenzene sulfonic acid (35%). A much higher amount of Orange II (~90×) was detected in the cell pellets from the active viable cells compared with those from boiled cells incubated with the same concentration of Orange II. This finding suggests that Orange II was primarily transported into the S. aureus cells for metabolism, instead of the theory that the azo dye metabolism occurs extracellularly. In addition, the metabolomics results showed that Sudan III affected energy pathways of the S. aureus cells, while Orange II had less noticeable effects on the cells. In summary, this study provided novel information regarding azo dye metabolism by the skin bacterium, the effects of azo dyes on the bacterial cells and the important role on the toxicity and/or inactivation of these compounds due to microbial metabolism.

The enrichment of specific pollutant-reducing consortium is usually required prior to the startup of biocathode bioelectrochemical system (BES) and the whole process is time consuming. To rapidly establish a non-specific functional biocathode, direct polar inversion from bioanode to biocathode is proposed in this study. Based on the diverse reductases and electron transfer related proteins of anode-respiring bacteria (ARB), the acclimated electrochemically active biofilm (EAB) may catalyze reduction of different aromatic pollutants. Within approximately 12 d, the acclimated bioanodes were directly employed as biocathodes for nitroaromatic nitrobenzene (NB) and azo dye acid orange 7 (AO7) reduction. Our results indicated that the established biocathode significantly accelerated the reduction of NB to aniline (AN) and AO7 to discolored products compared with the abiotic cathode and open circuit controls. Several microbes possessing capabilities of nitroaromatic/azo dye reduction and bidirectional electron transfer were maintained or enriched in the biocathode communities. Cyclic voltammetry highlighted the decreased over-potentials and enhanced electron transfer of biocathode as well as demonstrated the ARB Geobacter containing cytochrome c involved in the backward electron transfer from electrode to NB. This study offers new insights into the rapid establishment and modularization of functional biocathodes for the potential treatment of complicated electron acceptors-coexisting wastewaters., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Glutamate uptake into synaptic vesicles in nerve terminals is a pivotal step in glutamate synaptic transmission. Glutamate is the major excitatory neurotransmitter and, as such, the vesicular glutamate transporter (VGLUT) responsible for this uptake is involved in a variety of nervous system functions and various types of pathophysiology. As yet, no VGLUT-specific, membrane-permeable agents have been developed to affect neuronal function in intact neurons, although two potent VGLUTspecific inhibitors are known. These compounds contain diazo and highly charged sulfonic acid groups, rendering them membrane-impermeable and potentially cytotoxic. In an effort to eliminate these undesirable properties, we have developed two novel agents, Brilliant Yellow analogs 1 and 2, which are free of these two groups. We show here that these agents retain highly VGLUT-selective inhibitory activity, despite their reduction in potency, and exhibit no significant cellular toxicity. Potential use of this molecular modification is discussed.

Interleukin-22 (IL-22), a member of the IL-10 superfamily, plays essential roles in fighting against mucosal microbial infection and maintaining mucosal barrier integrity within the intestine. However, little knowledge exists on the ability of porcine IL-22 (pIL-22) to fight against viral infection in the gut. In this study, we found that recombinant mature pIL-22 (mpIL-22) inhibited the infection of multiple diarrhea viruses, including alpha coronavirus, porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine rotavirus (PoRV), in the intestinal porcine epithelial cell line J2 (IPEC-J2) cells. mpIL-22 up-regulated the expression of the antimicrobial peptide beta-defensin (BD-2), cytokine IL-18 and IFN-λ. Furthermore, we found that mpIL-22 induced phosphorylation of STAT3 on Ser727 and Tyr705 in IPEC-J2 cells. Inhibition of STAT3 phosphorylation by S3I-201 abrogated the antiviral ability of mpIL-22 and the mpIL-22-induced expression of BD-2, IL-18, and IFN-λ. Together, mpIL-22 inhibited the infection of PoRV and enteric coronaviruses, and up-regulated the expression of antimicrobial genes in IPEC-J2, which were mediated by the activation of the STAT3 signal pathway. The significant antiviral activity of IL-22 to curtail multiple enteric diarrhea viruses in vitro suggests that pIL-22 could be a novel therapeutic against devastating viral diarrhea in piglets., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This study shows the therapeutic outcome of Photochemical Internalisation (PCI) in prostate cancer in vitro surpasses that of Photodynamic Therapy (PDT) and could improve prostate PDT in the clinic, whilst avoiding chemotherapeutics side effects. In addition, the study assesses the potential of PCI with two different photosensitisers (TPCS 2a and TPPS 2a ) in prostate cancer cells (human PC3 and rat MatLyLu) using standard 2D monolayer culture and 3D biomimetic model. Photosensitisers were used alone for photodynamic therapy (PDT) or with the cytotoxin saporin (PCI). TPPS 2a and TPCS 2a were shown to be located in discrete cytoplasmic vesicles before light treatment and redistribute into the cytosol upon light excitation. PC3 cells exhibit a higher uptake than MatLyLu cells for both photosensitisers. In the 2D model, PCI resulted in greater cell death than PDT alone in both cell lines. In 3D model, morphological changes were also observed. Saporin-based toxicity was negligible in PC3 cells, but pronounced in MatLyLu cells (IC50 = 18 nM). In conclusion, the study showed that tumour features such as tumour cell growth rate or interaction with drugs determine therapeutic conditions for optimal photochemical treatment in metastatic prostate cancer., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Monoclonal antibodies labeled with near-infrared (NIR) fluorophores have potential use in disease detection, intraoperative imaging, and pharmacokinetic characterization of therapeutic antibodies in both the preclinical and clinical setting. Recent work has shown conjugation of NIR fluorophores to antibodies can potentially alter antibody disposition at a sufficiently high degree of labeling (DoL); however, other reports show minimal impact after labeling with NIR fluorophores. In this work, we label two clinically approved antibodies, Herceptin (trastuzumab) and Avastin (bevacizumab), with NIR dyes IRDye 800CW (800CW) or Alexa Fluor 680 (AF680), at 1.2 and 0.3 dyes/antibody and examine the impact of fluorophore conjugation on antibody plasma clearance and tissue distribution. At 0.3 DoL, AF680 conjugates exhibited similar clearance to unlabeled antibody over 17 days while 800CW conjugates diverged after 4 days, suggesting AF680 is a more suitable choice for long-term pharmacokinetic studies. At the 1.2 DoL, 800CW conjugates cleared faster than unlabeled antibodies after several hours, in agreement with other published reports. The tissue biodistribution for bevacizumab-800CW and -AF680 conjugates agreed well with literature reported biodistributions using radiolabels. However, the greater tissue autofluorescence at 680 nm resulted in limited detection above background at low (∼2 mg/kg) doses and 0.3 DoL for AF680, indicating that 800CW is more appropriate for short-term biodistribution measurements and intraoperative imaging. Overall, our work shows a DoL of 0.3 or less for non-site-specifically labeled antibodies (with a Poisson distribution) is ideal for limiting the impact of NIR fluorophores on antibody pharmacokinetics.

Slow growth of Mycobacterium tuberculosis, the causative agent of tuberculosis, hinders advancement in all areas of research toward prevention and treatment. Real-time imaging with reporter enzyme fluorescence (REF) that uses custom fluorogenic substrates for bacterial enzymes allows rapid and specific detection of M. tuberculosis in live animals. We have synthesized a novel REF substrate, CNIR800, that carries a near-infrared (NIR) fluorochrome IRDye 800CW, with a quencher connected through the lactam ring that is hydrolyzed by the enzyme BlaC (β-lactamase) that is naturally expressed by M. tuberculosis. CNIR800 produces long-wavelength emission at 795 nm upon excitation (745 nm) and exhibits significantly improved signal to noise ratios for detection of M. tuberculosis. The detection threshold with CNIR800 is approximately 100 colony-forming units (CFU) in vitro and <1000 CFU in the lungs of mice. Additionally, fluorescence signal from cleaved CNIR800 reaches maximal levels 4-6 hours after administration in live animals, allowing accurate evaluation of antituberculous drug efficacy. Thus, CNIR800 represents an excellent substrate for accurate detection of M. tuberculosis rapidly and specifically in animals, facilitating research toward understanding pathogenic mechanisms, evaluation of therapeutic outcomes, and screening new vaccines., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Citrus limon peroxidase mediated decolourization of Direct Yellow 4 (DY4) was investigated. The process variables (pH, temperature, incubation time, enzyme dose, H 2 O 2 amount, dye concentration, co-metal ions and surfactants) were optimized for maximum degradation of dye. Maximum dye decolourization of 89.47% was achieved at pH 5.0, temperature 50 °C, enzyme dose 24 U/mL, H 2 O 2 concentration 0.25 mM and DY4 concentration 18.75 mg/L and incubation time 10 min. The co-metal ions and surfactants did not affect the dye decolourization significantly. Response surface analysis revealed that predicted values were in agreement with experimentally determined responses. The degradation products were identified by UPLC/MS analysis and degradation pathway was proposed. Besides, phytotoxicity assay revealed a considerable detoxification in response of biodegradation of DY4 dye. C. limon showed promising efficiency for DY4 degradation and could possibly be used for the remediation of textile effluents., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Biocathodes may be a suitable replacement of platinum in microbial fuel cells (MFCs) if the cost of MFCs is to be reduced. However, the use of enzymes as bio-cathodes is fraught with loss of activity as time progresses. A possible cause of this loss in activity might be pH increase in the cathode as pH gradients in MFCs are well known. This pH increase is however, accompanied by simultaneous increase in salinity; therefore salinity may be a confounding variable. This study investigated various ways of mitigating pH changes in the cathode of MFCs and their effect on laccase activity and decolourisation of a model azo dye Acid orange 7 in the anode chamber. Experiments were run with catholyte pH automatically controlled via feedback control or by using acetate buffers (pH 4.5) of various strength (100mM and 200mM), with CMI7000 as the cation exchange membrane. A comparison was also made between use of CMI7000 and Nafion 117 as the transport properties of cations for both membranes (hence their potential effects on pH changes in the cathode) are different. Results show that using Nafion 117 membrane limits salinity and pH changes in the cathode (100mM acetate buffer as catholyte) leading to prolonged laccase activity and faster AO7 decolourisation compared to using CMI7000 as a membrane; similarly automatic pH control in the cathode chamber was found to be better than using 200mM acetate buffer. It is suggested that while pH control in the cathode chamber is important, it does not guarantee sustained laccase activity; as salinity increases affect the activity and it could be mitigated using a cation selective membrane., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In order to regulate the skin permeation rate (flux) of escitalopram (ESP), ion-pair strategy was used in our work. Five organic acids with different physicochemical properties, benzoic acid (BA), ibuprofen (IB), salicylic acid (SA), benzenesulfonic acid (BSA), and p-aminobenzoic acid (PABA), were employed as counter-ions to regulate the permeation rate of ESP across the rabbit abdominal skin in vitro. The interaction between ESP and organic acids was characterized by FTIR and 13 C NMR spectroscopy. Results showed that all organic acids investigated in this study performed a controlling effect on ESP flux. To further analyze the factors concerned with the permeation capability of ESP-acid complex, a multiple linear regression model was used. It is concluded that the steady-state flux (J) of ESP-acid complexes had a positive correlation with log K o/w (the n-octanol/water partition coefficient of ion-pair complex) and pK a (the acidity of organic acid counter-ion), but a negative correlation with MW (the molecular weight of ion-pair complex). The logK o/w of ion-pair complex is the primary one in all the factors that influence the skin permeation rate of ESP. The results demonstrated that organic acid with appropriate physicochemical properties can be considered as suitable candidate for the transdermal drug delivery of escitalopram.

Aluminum in human brain tissue is implicated in the etiologies of neurodegenerative diseases including Alzheimer's disease. While methods for the accurate and precise measurement of aluminum in human brain tissue are widely acknowledged, the same cannot be said for the visualization of aluminum. Herein we have used transversely-heated graphite furnace atomic absorption spectrometry to measure aluminum in the brain of a donor with Alzheimer's disease, and we have developed and validated fluorescence microscopy and the fluor lumogallion to show the presence of aluminum in the same tissue. Aluminum is observed as characteristic orange fluorescence that is neither reproduced by other metals nor explained by autofluorescence. This new and relatively simple method to visualize aluminum in human brain tissue should enable more rigorous testing of the aluminum hypothesis of Alzheimer's disease (and other neurological conditions) in the future.

Polyaniline is a conductive polymer with distinctive optical and electrical properties. Its enzymatic synthesis is an environmentally friendly alternative to the use of harsh oxidants and extremely acidic conditions. 7D5L, a high-redox potential laccase developed in our lab, is the biocatalyst of choice for the synthesis of green polyaniline (emeraldine salt) due to its superior ability to oxidize aniline and kinetic stability at the required polymerization conditions (pH 3 and presence of anionic surfactants) as compared with other fungal laccases. Doses as low as 7.6 nM of 7D5L catalyze the polymerization of 15 mM aniline (in 24 h, room temperature, 7% yield) in the presence of different anionic surfactants used as doping templates to provide linear and water-soluble polymers. Aniline polymerization was monitored by the increase of the polaron absorption band at 800 nm (typical for emeraldine salt). Best polymerization results were obtained with 5 mM sodium dodecylbenzenesulfonate (SDBS) as template. At fixed conditions (15 mM aniline and 5mM SDBS), polymerization rates obtained with 7D5L were 2.5-fold the rates obtained with commercial Trametes villosa laccase. Moreover, polyaniline yield was notably boosted to 75% by rising 7D5L amount to 0.15 μM, obtaining 1g of green polyaniline in 1L-reaction volume. The green polymer obtained with the selected system (7D5L/SDBS) holds excellent electrochemical and electro-conductive properties displayed in water-dispersible nanofibers, which is advantageous for the nanomaterial to be readily cast into uniform films for different applications., Competing Interests: Novozymes’ participation does not alter our adherence to all PLOS ONE policies on sharing data and materials.

To ensure the optimal performance of oral controlled release formulations, drug colon permeability is one of the critical parameters. Consequently developing this kind of formulations for low permeability molecules requires strategies to increase their ability to cross the colonic membrane. The objective of this work is to show if an ion-pair formation can improve the colon permeability of atenolol as a low permeability drug model. Two counter ions have been tested: brilliant blue and bromophenol blue. The Distribution coefficients at pH7.00 (DpH7) of atenolol, atenolol + brilliant blue and atenolol + bromophenol blue were experimentally determined in n-octanol. Moreover, the colonic permeability was determined in rat colon using in situ closed loop perfusion method based in Doluisio's Technique. To check the potential effects of the counter ions on the membrane integrity, a histological assessment of colonic tissue was done. The results of the partitioning studies were inconclusive about ion-pair formation; nevertheless colon permeability was significantly increased by both counter ions (from 0.232±0.021cm/s to 0.508±0.038cm/s in the presence of brilliant blue and to 0.405±0.044cm/s in the presence of bromophenol blue). Neither damage on the membrane was observed on the histological studies, nor any change on paracellular permeability suggesting that the permeability enhancement could be attributed to the ion-pair formation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The synergistic technique of pulsed discharge plasma (PDP) and activated carbon (AC) was built to investigate the kinetics of acid orange 7 (AO7) degradation under different conditions of AC addition, electrode gap, initial pH value of solution, gas variety and gas flow rate. Emission spectra of OH and O, UV-vis absorption spectra of the AO7 solution and TOC removal were measured to illustrate the synergistic mechanism of the PDP and the AC. The obtained results indicated that the kinetic constant of AO7 degradation increased from 0.00947 min(-1) to 0.01419 min(-1) when 4 g AC was added into the PDP system; AO7 degradation was higher in the case of alkaline solution when oxygen was used as the flow gas in the PDP/AC system, 2 L/min oxygen flow was more favorable for the degradation. Results of the relative emission intensities of OH and O indicated the catalytic effect of the AC on the active species formation as well as the important role of the two radicals for the AO7 degradation. There was no new peaks appeared by the UV-vis analysis of the AO7 solution after 60 min treatment. The highest TOC removal in the PDP/AC system was 30.3%, which was achieved under the condition of 4 L/min air flow rate and 3 initial pH value., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Unlabelled: Although Mn(2+) is the most abundant substrate of versatile peroxidases (VPs), repression of Pleurotus ostreatus vp1 expression occurred in Mn(2+)-sufficient medium. This seems to be a biological contradiction. The aim of this study was to explore the mechanism of direct oxidation by VP1 under Mn(2+)-deficient conditions, as it was found to be the predominant enzyme during fungal growth in the presence of synthetic and natural substrates. The native VP1 was purified and characterized using three substrates, Mn(2+), Orange II (OII), and Reactive Black 5 (RB5), each oxidized by a different active site in the enzyme. While the pH optimum for Mn(2+) oxidation is 5, the optimum pH for direct oxidation of both dyes was found to be 3. Indeed, effective in vivo decolorization occurred in media without addition of Mn(2+) only under acidic conditions. We have determined that Mn(2+) inhibits in vitro the direct oxidation of both OII and RB5 while RB5 stabilizes both Mn(2+) and OII oxidation. Furthermore, OII was found to inhibit the oxidation of both Mn(2+) and RB5. In addition, we could demonstrate that VP1 can cleave OII in two different modes. Under Mn(2+)-mediated oxidation conditions, VP1 was able to cleave the azo bond only in asymmetric mode, while under the optimum conditions for direct oxidation (absence of Mn(2+) at pH 3) both symmetric and asymmetric cleavages occurred. We concluded that the oxidation mechanism of aromatic compounds by VP1 is controlled by Mn(2+) and pH levels both in the growth medium and in the reaction mixture., Importance: VP1 is a member of the ligninolytic heme peroxidase gene family of the white rot fungus Pleurotus ostreatus and plays a fundamental role in biodegradation. This enzyme exhibits a versatile nature, as it can oxidize different substrates under altered environmental conditions. VPs are highly interesting enzymes due to the fact that they contain unique active sites that are responsible for direct oxidation of various aromatic compounds, including lignin, in addition to the well-known Mn(2+) binding active site. This study demonstrates the limits of versatility of P. ostreatus VP1, which harbors multiple active sites, exhibiting a broad range of enzymatic activities, but they perform differently under distinct conditions. The versatility of P. ostreatus and its enzymes is an advantageous factor in the fungal ability to adapt to changing environments. This trait expands the possibilities for the potential utilization of P. ostreatus and other white rot fungi., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

A novel bioflocculant MBF057 produced by a salt-tolerant Haloplanus vescus HW0579 was investigated in this study. The effects of culture conditions such as initial pH, inoculum size, and chemical oxygen demand (COD) of K-acid wastewater on MBF0579 production were studied. The result showed that 8.09 g/L purified MBF0579 was extracted with the following optimized conditions: 780 mg/L COD of K-acid wastewater as carbon source, inoculum size 12.5%, and initial pH 7.0. The biopolymer contained 78.6% polysaccharides and 21.1% proteins. The highest flocculating rate of 81.86 and 95.07% for the COD and chroma of acid brilliant scarlet gelb rot (yellow/red, GR) dye wastewater were achieved at a dosage of 150 mg/L, pH 2.0 and contact time 100 min. Overall, these findings indicate bioflocculation offers an effective alternative method of decreasing acid brilliant scarlet GR during dye wastewater treatment.

Mass transfer and biological transformation phenomena in the capillary fringe were studied using phenol, salicylic acid, benzenesulfonic acid, and the iodinated X-ray contrast agent iomeprol as model organic compounds and the microorganism strain Pseudomonas fluorescens. Three experimental approaches were used: Batch experiments (uniform water saturation and transport by diffusion), in static columns (with a gradient of water saturation and advective transport in the capillaries) and in a flow-through cell (with a gradient of water saturation and transport by horizontal and vertical flow: 2-dimension flow-through microcosm). The reactors employed for the experiments were filled with quartz sand of defined particle size distribution (dp=200...600 μm, porosity ε=0.42). Batch experiments showed that phenol and salicylic acid have a high, whereas benzenesulfonic acid and iomeprol have a quite low potential for biodegradation under aerobic conditions and in a matrix nearly close to water saturation. Batch experiments under anoxic conditions with nitrate as electron acceptor revealed that the biodegradation of the model compounds was lower than under aerobic conditions. Nevertheless, the experiments showed that the moisture content was also responsible for an optimized transport in the liquid phase of a porous medium. Biodegradation in the capillary fringe was found to be influenced by both the moisture content and availability of the dissolved substrate, as seen in static column experiments. The gas-liquid mass transfer of oxygen also played an important role for the biological activity. In static column experiments under aerobic conditions, the highest biodegradation was found in the capillary fringe (e.g. βt/β0 (phenol)=0 after t=6 d) relative to the zone below the water table and unsaturated zone. The highest biodegradation occurred in the flow-through cell experiment where the height of the capillary fringe was largest., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A single crystal charge transfer (CT) complex, 2-aminopyridinium-4-methylbenzenesulfonate (APTS) was synthesized and recrystallized by slow solvent evaporation solution growth method at room temperature. The complex has been characterized with the elemental analysis, UV-visible, infrared (IR), (1)H and (13)C nuclear magnetic resonance (NMR) spectra. Thermogravimetric (TG) and differential thermal analysis (DTA) were reported the thermal behaviour of the complex. Single crystal XRD studies showed that the orthorhombic nature of the crystal with space group Pbca. The biological activities of CT complex, such as DNA binding and antioxidant activity has been carried out. The results indicated that the compound could interact with DNA through intercalation and show significant capacity of scavenging with 2,2-diphenyl-2-picryl-hydrazyl (DPPH)., (Copyright © 2015. Published by Elsevier B.V.)