Positive effects of retrofitting MBBR and IFAS systems into MBRs can be exploited by introducing chemical enhancement applying coagulants in the membrane separation step. The current study reports basic principles of chemical enhancement with aluminium sulphate coagulant in biofilm-MBR (Bf-MBR) based on results of total recycle tests performed at different dosages of the chemical enhancer and properties characterization of filtrates, supernatants and sediments. It demonstrates a possibility to achieve lower membrane fouling rates with dosing of aluminium sulphate coagulant into MBBR and IFAS mixed liquors by extending operational cycles by 20 and 80 time respectively as well as increasing operating permeability of membrane separation by 1.3 times for IFAS. It has been found that charge neutralization is the dominating mechanism of aluminium sulphate action as a chemical enhancer in Bf-MBR, however, properties of the membrane surface influencing charge repulsion of foulants should be considered together with the secondary ability of the coagulant to improve consolidation of sediments. Full article

Plasma electrolytic oxidation (PEO) coatings were grown on AZ31 Mg alloy in a silicate-based electrolyte containing KF using unipolar and bipolar (usual and soft-sparking) waveforms. The coatings were dual-layered consisting of MgO, MgF₂ and Mg₂SiO₄ phases. Surface morphology of the coatings was a net-like (scaffold) containing a micro-pores network, micro-cracks and granules of oxide compounds. Deep pores were observed in the coating produced by unipolar and usual bipolar waveforms. The soft-sparking eliminated the deep pores and produced the lowest porosity in the coatings. It was found that the corrosion performance of the coatings evaluated using EIS in 3.5 wt. % NaCl solution is mostly determined by the inner layer resistance, because of its higher compactness. After 4 days of immersion, the inner layer resistances were almost the same for all coatings. However, the coatings produced by unipolar and usual bipolar waveforms showed sharp decays in inner layer resistances after 1 week and even the barrier effect of outer layer was lost for the unipolar-produced coating after 3 weeks. The low-frequency inductive loops appeared after a 3-week immersion for all coatings indicated that the substrate was under local corrosion attack. However, both coatings produced by soft-sparking waveforms provided the highest corrosion performance. Full article

High dietary levels of molybdenum (MO) can negatively affect productive performances and health status of laying hens, while tea polyphenol (TP) can mitigate the negative impact of high MO exposure. However, our understanding of the changes induced by TP on MO challenged layers performances and oxidative status, and on the microbiota, remains limited. The aim of the present study was to better understand host (performances and redox balance) and microbiota responses in MO-challenged layers with dietary TP. In this study, 200 Lohmann laying hens (65-week-old) were randomly allocated in a 2 × 2 factorial design to receive a diet with or without MO (0 or 100 mg/kg), and supplemented with either 0 or 600 mg/kg TP. The results indicate that 100 mg/kg MO decreased egg production (p = 0.03), while dietary TP increased egg production in MO challenged layers (p < 0.01). Egg yolk color was decreased by high MO (p < 0.01), while dietary TP had no effect on yolk color (p > 0.05). Serum alanine transaminase (ALT), aspartate aminotransferase (AST), and malonaldehyde (MDA) concentration were increased by high MO, while total antioxidant capacity (T-AOC), xanthine oxidase (XOD) activity, glutathione s-transferase (GSH-ST), and glutathione concentration in serum were decreased (p < 0.05). Dietary TP was able to reverse the increasing effect of MO on ALT and AST (p < 0.05). High MO resulted in higher MO levels in serum, liver, kidney, and egg, but it decreased Cu and Se content in serum, liver, and egg (p < 0.05). The Fe concentration in liver, kidney, and eggs was significantly lower in MO supplementation groups (p < 0.05). High MO levels in the diet led to lower Firmicutes and higher Proteobacteria abundance, whereas dietary TP alone and/or in high MO treatment increased the Firmicutes abundance and the Firmicutes/Bacteroidetes ratio at phylum level. High MO increased the abundance of Proteobacteria (phylum), Deltaproteobacteria (class), Mytococcales (order), and Nanocystaceae (family), whereas dietary TP promoted the enrichment of Lactobacillus agilis (species). Dietary TP also enhanced the enrichment of Bacilli (class), Lactobacillates (order), Lactobacillus (family), and Lactobacillus gasseri (species). Microbiota analysis revealed differentially enriched microbial compositions in the cecum caused by MO and TP, which might be responsible for the protective effect of dietary TP during a MO challenge. Full article

Terbinafine (TBF) is commonly used in the management of fungal infections of the skin because of its broad spectrum of activity. Currently, formulations containing the free base and salt form are available. However, there is only limited information in the literature about the physicochemical properties of this drug and its uptake by the skin. In this work, we conducted a comprehensive characterisation of TBF, and we also examined its percutaneous absorption in vitro in porcine skin. TBF-free base was synthesised from the hydrochloride salt by a simple proton displacement reaction. Both the free base and salt form were further analysed using Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA). Delivery of TBF-free base in excised porcine skin was investigated from the following solvents: Isopropyl myristate (IPM), propylene glycol monolaurate (PGML), Transcutol^® (TC), propylene glycol (PG), polyethylene glycol 200 (PEG 200), oleic acid (OL), ethanol (EtOH), and isopropyl alcohol (IPA). Permeation and mass balance studies confirmed that PG and TC were the most efficacious vehicles, delivering higher amounts of TBF-free base to the skin compared with a commercial gel (p < 0.05). These preliminary results are promising and will inform the development of more complex formulations in future work. Full article

A major limitation of clinically used cancer drugs is the lack of specificity resulting in toxicity. To address this, we performed a phenotypically-driven screen to identify optimal multidrug combinations acting with high efficacy and selectivity in clear cell renal cell carcinoma (ccRCC). The search was performed using the Therapeutically Guided Multidrug Optimization (TGMO) method in ccRCC cells (786-O) and nonmalignant renal cells and identified a synergistic low-dose four-drug combination (C2) with high efficacy and negligible toxicity. We discovered that C2 inhibits multipolar spindle pole clustering, a survival mechanism employed by cancer cells with spindle abnormalities. This phenotype was also observed in 786-O cells resistant to sunitinib, the first line ccRCC treatment, as well as in melanoma cells with distinct percentages of supernumerary centrosomes. We conclude that C2-treatment shows a high efficacy in cells prone to form multipolar spindles. Our data suggest a highly effective and selective C2 treatment strategy for malignant and drug-resistant cancers. Full article

Chemometrics is the chemistry field responsible for planning and extracting the maximum of information of experiments from chemical data using mathematical tools (linear algebra, statistics, and so on). Active pharmaceutical ingredients (APIs) can form impurities when exposed to excipients or environmental variables such as light, high temperatures, acidic or basic conditions, humidity, and oxidative environment. By considering that these impurities can affect the safety and efficacy of the drug product, it is necessary to know how these impurities are yielded and to establish the pathway of their formation. In this context, forced degradation studies of pharmaceutical drugs have been used for the characterization of physicochemical stability of APIs. These studies are also essential in the validation of analytical methodologies, in order to prove the selectivity of methods for the API and its impurities and to create strategies to avoid the formation of degradation products. This review aims to demonstrate how forced degradation studies have been actually performed and the applications of chemometric tools in related studies. Some papers are going to be discussed to exemplify the chemometric applications in forced degradation studies. Full article

The dried roots of Euphorbia kansui S.L.Liou ex S.B.Ho have long been used to treat edema in China. However, the severe toxicity caused by Euphorbia kansui (EK) has seriously restricted its clinical application. Although EK was processed with vinegar to reduce its toxicity, the detailed mechanisms of attenuation in toxicity of EK stir-fried with vinegar (VEK) have not been well delineated. Diterpenoids are the main toxic ingredients of EK, and changes in these after processing may be the underlying mechanism of toxicity attenuation of VEK. 3-O-(2′E,4′Z-decadienoyl)-20-O-acetylingenol (3-O-EZ) is one of the diterpenoids derived from EK, and the content of 3-O-EZ was significantly reduced after processing. This study aims to explore the underlying mechanisms of toxicity reduction of VEK based on the change of 3-O-EZ after processing with vinegar. Based on the chemical structure of 3-O-EZ and the method of processing with vinegar, simulation experiments were carried out to confirm the presence of the product both in EK and VEK and to enrich the product. Then, the difference of peak area of 3-O-EZ and its hydrolysate in EK and VEK were detected by ultra-high-performance liquid chromatography (UPLC). Furthermore, the toxicity effect of 3-O-EZ and its hydrolysate, as well as the underlying mechanism, on zebrafish embryos were investigated. The findings showed that the diterpenoids (3-O-EZ) in EK can convert into less toxic ingenol in VEK after processing with vinegar; meanwhile, the content of ingenol in VEK was higher than that of EK. More interestingly, the ingenol exhibited less toxicity (acute toxicity, developmental toxicity and organic toxicity) than that of 3-O-EZ, and 3-O-EZ could increase malondialdehyde (MDA) content and reduce glutathione (GSH) content; cause embryo oxidative damage by inhibition of the succinate dehydrogenase (SDH) and superoxide dismutase (SOD) activity; and induce inflammation and apoptosis by elevation of IL-2 and IL-8 contents and activation of the caspase-3 and caspase-9 activity. Thus, this study contributes to our understanding of the mechanism of attenuation in toxicity of VEK, and provides the possibility of safe and rational use of EK in clinics. Full article

In China, the Returning Farmland to Forest Program (RFFP) has afforested large areas, transforming land and livelihoods. By impacting vegetation cover, it may also drive spatial pattern changes across landscapes. Most studies have focused on time series data as a means to determine the effectiveness of the program, but there is a paucity of community-level comparative studies. Twelve communities in Northwest Yunnan Province were selected to test whether the RFFP changed landscape patterns by testing the following hypotheses: with (or without) the RFFP, forest and shrubland fragmentations would decrease (or increase) and farmland fragmentation would increase (or decrease). Remote sensing images from 2000, 2010, and 2014 were used to compare the differences in landscape patterns. Survey data from 421 households were used to examine the socioeconomic and ecological factors that affect the differences in landscape fragmentation across communities. The results showed that landscape patterns and fragmentation metrics were not significantly different between communities with or without the RFFP, regardless of the class or landscape level. These communities showed consistent patterns of change in their fragmentation parameters between 2000 and 2014, with forest fragmentation decreasing and the fragmentation of farmland and the overall landscape increasing. The regression models suggest these changes were affected by the local natural conditions, socioeconomic patterns, policy implementation, and farmer livelihoods, with the proximity to market towns and elevation being significant factors. The RFFP alone did not directly drive the changes in landscape patterns for the considered region. For the new RFFP to effectively contribute to reducing fragmentation, managers of afforestation efforts should carefully consider livelihoods and biophysical factors that influence changes in landscape patterns. Full article

Non-invasive imaging of cyclooxygenase-2 (COX-2) by radiolabeled ligands is attractive for the diagnosis of cancer, and novel highly affine leads with optimized pharmacokinetic profile are of great interest for future developments. Recent findings have shown that methylsulfonyl-substituted (dihydro)pyrrolo[3,2,1-hi]indoles represent highly potent and selective COX-2 inhibitors but possess unsuitable pharmacokinetic properties for radiotracer applications. Based on these results, we herein present the development and evaluation of a second series of sulfonamide-substituted (dihydro)pyrrolo[3,2,1-hi]indoles and their conversion into the respective more hydrophilic N-propionamide-substituted analogs. In comparison to the methylsulfonyl-substituted leads, COX inhibition potency and selectivity was retained in the sulfonamide-substituted compounds; however, the high lipophilicity might hinder their future use. The N-propionamide-substituted analogs showed a significantly decreased lipophilicity and, as expected, lower or no COX-inhibition potency. Hence, the N-(sulfonyl)propionamides can be regarded as potential prodrugs, which represents a potential approach for more sophisticated radiotracer developments. Full article

Characterization of heterogeneous materials, such as particles from mechanically processed waste printed circuit boards, is a challenging task. The majority of characterization methods either give average information or information that is very limited and in a tiny area of specific interest. That said, capturing such heterogeneity is significantly important for any kind of processes. Degree of liberation, indicating how much the target component is liberated from the non-valuable components, is a key property to determine the success of subsequent process for valuable material recovery. This work analyzed the degree of liberation of metals within the products of hammer milling process via the combination of image acquisition and analysis. The digital microscope and a scanning electron microscope (SEM) coupled with the energy dispersive spectroscopy (EDS) were used for image acquisition and elemental mapping, in order to evaluate the selective liberation under different milling conditions (i.e., feed mass, milling time) for different metals (mainly Cu and Al) and particle size fractions. The obtained liberation degree was also modelled and determined the liberation parameters that were compared. The results showed that the degree of liberation significantly depend on the milling conditions and metals we analyzed, and well correlated with the selective metal enrichment behavior. Results between the two methods showed some similarities and discrepancies. The advantages and disadvantages of the above two methods were identified and discussed in the paper, in addition to their methodological developments. Full article

Lighting in heritage is complex because of the forms intervening in it. The historical evolution of cultures has not been analytical and therefore, the shapes involved differ greatly from the cuboids typically found in 21st century architecture. As a vector, light inevitably attaches to surface sources. In this research, we focused on 3D curved geometries. Following a different trail to radiative transfer by virtue of detailed knowledge of the spatiality of volumes, we present new expressions, previously undefined in the literature, that are derived from a combination of surfaces that we have found in many archaeological sites around Asia. In the discussion, we start from the particularities of spherical surfaces where a normal vector has to pass through the center. By means of easy calculations, we deducted innovative laws. These in turn, allowed us to formulate several new expressions for configuration factors based on the adroit use of spherical fragments. The method easily extends to organic shapes that are often contained in the sustainable architecture of the past. The method finishes with suitable algorithms to assess the reflections in such curved forms. Finally, we implemented the results in our creative software. In this way, we enhanced the sustainable paradigms for heritage structures in Asia that we present as a conclusion of the article. Full article

The Sistan Basin has been recognized as one of the most active dust sources and windiest desert environments in the world. Although the dust activity in Sistan maximizes during the summer, rare but intense dust storms may also occur in the winter. This study aims to elucidate the atmospheric dynamics related to dust emission and transport, dust-plume characteristics, and impacts on aerosol properties and air quality during an intense dust storm over Sistan in February 2019. The dust storm was initiated by strong northerly winds (~20 ms⁻¹) associated with the intrusion of a cold front from high latitudes. The upper-level potential vorticity (PV)-trough evolved into a cut-off low in the mid and upper troposphere and initiated unstable weather over Afghanistan and northern Pakistan. At the surface, density currents emanating from deep convective clouds and further strengthened by downslope winds from the mountains, caused massive soil erosion. The passage of the cold front reduced the temperature by ~10 °C and increased the atmospheric pressure by ~10 hPa, while the visibility was limited to less than 200 m. The rough topography played a major role in modulating the atmospheric dynamics, wind field, dust emissions, and transport pathways. Meso-NH model simulates large amounts of columnar mass dust loading (> 20 g m⁻²) over Sistan, while the intense dust plume was mainly traveling below 2 km and increased the particulate matter (PM₁₀) concentrations up to 1800 µg m⁻³ at Zabol. The dust storm was initially moving in an arc-shaped pathway over the Sistan Basin and then it spread away. Plumes of dust covered a large area in southwest Asia, reaching the northern Arabian Sea, and the Thar desert one to two days later, while they strongly affected the aerosol properties at Karachi, Pakistan, by increasing the aerosol optical depth (AOD > 1.2) and the coarse-mode fraction at ~0.7. Full article