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In light of the intriguing potential of anti-angiogenic approach in suppressing choroidal neovascularization, we attempted to elaborate synthetic gene delivery systems encapsulating anti-angiogenic plasmid DNA as alternatives of clinical antibody-based therapeutics. Herein, block copolymer of cyclic Arg-Gly-Asp-poly(ethylene glycol)-poly(lysine-thiol) [RGD-PEG-PLys(thiol)] with multifunctional components was tailored in manufacture of core-shell DNA delivery nanoparticulates. Note that the polycationic PLys segments were electrostatically complexed with anionic plasmid DNA into nanoscaled core, and the tethered biocompatible PEG segments presented as the spatial shell (minimizing non-specific reactions in biological milieu). Furthermore, the aforementioned self-assembly was introduced with redox-responsive disulfide crosslinking due to the thiol coupling. Hence, reversible stabilities, namely stable in extracellular milieu but susceptible to disassemble for liberation of the DNA payloads in intracellular reducing microenvironment, were verified to facilitate transcellular gene transportation. In addition, RGD was installed onto the surface of the proposed self-assemblies with aim of targeted accumulation and internalization into angiogenic endothelial cells given that RGD receptors were specifically overexpressed on their cytomembrane surface. The proposed anti-angiogenic DNA therapeutics were validated to exert efficient expression of anti-angiogenic proteins in endothelial cells and elicit potent inhibition of ocular neovasculature post intravitreous administration. Hence, the present study approved the potential of gene therapy in treatment of choroidal neovascularization. In light of sustainable gene expression properties of DNA therapeutics, our proposed synthetic gene delivery system inspired prosperous potentials in long-term treatment of choroidal neovascularization, which should be emphasized to develop further towards clinical translations., Graphical abstract Image, graphical abstract

Summary Catalytic reactions that convert green or sustainable starting materials into important classes of chemical compounds, generate hydrogen, and are mediated by Earth-abundant element catalysts are highly desirable. Here, we report on a catalytic dehydrogenative rearrangement of esters into 1,3-diketones. Esters are green or sustainable and inexpensive starting materials that are available in great diversity, and 1,3-diketones are highly attractive building blocks for organic synthesis. The concerted interaction of a base-acid catalyst and a dehydrogenation catalyst mediates our reaction. The dehydrogenation catalyst is based on manganese, and the hydrogen formed can be liberated and is the only by-product formed.

Recent results of Concepcion's group (Chem. Commun. 2015, 51, 4105) on water oxidation catalysis (WOC) by a ruthenium complex suggest that, at pH = 8, O2 release takes place after formation of a rhomboid bis(μ-oxo)-RuV2 species and not after generation of the typical µ-η1:η1-peroxo-RuIV2 intermediate, coming from the coupling of two RuV=O moieties (I2M mechanism), which is widely accepted to be formed at pH = 1. To analyze the differences between the reaction mechanisms of this WOC at different pHs, we performed DFT calculations of the full mechanism at pH = 1 and 8 of the WOC process catalyzed by the 2,2'-bipyridine-6,6'-dicarboxylate Ru complex. At pH = 8, we found that barriers leading to the hypothetic formation of rhombic RuV2O2 species are higher than those involved in the canonical I2M mechanism. The rate determining step at the latter pH is found to be the dimer formation while the bond cleavage for the O2 liberation process is barrierless. The computational results confirm that the most common I2M mechanism is preferred at both pHs, as the new proposal comprising formation of bis(μ-oxo)-RuV2 species involves higher energy barriers J.A.L.U. thanks Universitat de Girona for a IFUdG2017 PhD fellowship. A.P. is a Serra Húnter Fellow. A.P. and M.S. thank the Spanish MINECO for projects CTQ2014-59832-JIN and CTQ2017-85341, respectively. M.S. thanks the Generalitat de Catalunya for project 2017SGR39, the Xarxa de Referència en Química Teòrica i Computacional, and ICREA Academia 2014 prize

Liberation and reduction of cathode material are the necessary procedures for improving the recycling efficiency of cathode material derived from spent lithium-ion batteries. In this research work, a pyrolysis technology was utilized to remove the organic binder and enhance liberation of electrode materials. At the same time, pyrolysis treatment can facilitate the thermal-reduction of Co3+ in LiCoO2 to Co2+ with surface organics, which lays a foundation for the subsequent reductant-free acid leaching. Results indicate that the crystal structure of pure LiCoO2 is not changed at a pyrolysis temperature of 600 °C, but LiCoO2 transforms to CoO, Li2CO3, LiF, and Li2O under the reduction action of HF, pyrolytic carbon, and additive carbon black. Water-impact crushing is synchronized with water-leaching to separate electrode materials from aluminum foil and recover Li element. Afterwards, reductant-free acid leaching technology can be utilized to recycle Li and Co from spent LiCoO2 batteries. Recovery efficiency of Li element in water-leaching process was up to 92.17% while the remaining 7.83% of Li and all Co elements were recovered during reductant-free acid leaching process. Based on the foundation analysis, the green chemical process for recovering valuable metals from spent lithium-ion batteries was proposed.

Crushing is the key part for the recycling technology of waste printed circuit boards (WPCBs). In this study, the breakage and liberation effects of WPCBs was improved by heat pretreatment technology before crushing (HPBC). Based on the test results, 200 °C was found as the safe temperature for the HPBC of WPCBs. The fracture mode, particle size distribution, and enrichment characteristics of WPCBs were systematically studied. The experimental results show that the HPBC changed the breakage mode from longitudinal fracture to horizontal fracture and improved the liberation of metal from non-metal components. During the crushing process, the increase in the heat pretreatment time (30–120 min) and temperature (100–200 °C) can improve the crushing effect of WPCBs and increase the content of crushing products of −0.3 mm by 3.16% and 5.64%, respectively. Compared to the non-metallic components, the metal components have ductility and are difficult to break into −0.3 mm during the crushing process. HPBC can promote copper enrichment to narrow grain size. In the 0.3–1 mm range, the content of copper increased from 47.87% to 57.61%, an increase by 9.74%. The initial enrichment of copper was achieved by adjusting the crushing time. The recovery rate of copper can reach 85.66%, and the enrichment rate is 1.74 when 0.3–2 mm breaking product is used as enrichment. Therefore, HPBC can effectively improve the crushing and liberation effect of WPCBs and improve the enrichment rate, and thus is an effective pretreatment method.

This work aimed to develop and propose methods for evaluating the metal degree of liberation to characterize the metal deportment/concentration and liberation/association of mechanically processed waste Printed Circuit Boards (PCBs) that hold the complex and heterogeneity structure and metal distribution/association. Waste PCBs passed through a series of mechanical processing (i.e. comminution, sieving) for the metal recovery were characterized to understand and to evaluate the metal distribution and degree of liberation of the metals in order to optimize the comminution process, avoiding excessive fine particle production. The characterizations were performed at laboratory scale, as well as utilizing large scale experimental facilities, i.e. a portable X-Ray Fluorescence (XRF), micro-XRF and Synchrotron X-Ray Tomography. The proposed methods confirmed that metal liberation was very high in the fine size fraction (0.125–0.350 mm) while many locked particles were identified in the coarse size fraction (0.350–0.500 mm). Such results were analyzed and were discussed in order to better understand metal deportment/concentration behaviors. The advantages and disadvantages related to the different characterization approaches were identified and discussed in this paper, as well as their methodological developments in a waste PCBs’ mechanical processing perspective.

The light-emitting diode (LED) is considered a therapeutic tool due to its anti-inflammatory, analgesic, and wound-healing effects, which occur through angiogenesis, decrease in IL-1β and IL-6 secretion, and acceleration of the cicatricial process. Snakebites are an important public health problem in tropical regions of the world. LED treatment is a therapeutic tool associated with serum therapy used to minimize the local effects of snakebites, including decrease in creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations, myonecrosis, and inflammatory and haemorrhagic responses. In this study, we analysed the photobiomodulation effect of LED on the activation of murine macrophages induced by BthTX-I or BthTX-II isolated from Bothrops jararacussu venom. Photobiomodulation caused an increase in mitochondrial metabolism and a considerable decrease in cytotoxicity in murine macrophages. Moreover, it induced a decrease in reactive oxygen species and nitrogen liberation. However, photobiomodulation caused an increase in macrophage phagocytic capacity and lipid droplet formation. The results of this study corroborated with those of others in an unprecedented way and provide a better understanding of the mechanism of action of photobiomodulation, besides offering a coadjuvant action treatment for the local effects of snakebites, not achieved with serum therapy alone.

Determination of liberation spectrums by using MLA and QEMSCAN techniques require polished sections and fine particles. These techniques cannot be performed in-situ and for coarse particles. Thus, the focus of this technical note is to investigate whether the image analysis method can be used for the determination of liberation spectrum for coarse particles. Two methods were used to determine the liberation spectrum. In the first method, the liberation spectrum was obtained using the small and large diameter of particles. In the second method, the liberation spectrum was determined using the small and large diameter of particles as well as the shape correction diameter. The results showed that the image analysis can be used to successfully determine the liberation spectrum. The composition of composite particles was significantly improved when the stereological correction was used i.e. the square root of the mean square error for the particle composition using the method 1 was 1.25% while that using the method 2 was 0.60%. The proposed method might be used for the determination of liberation spectrum of high-grade real coarse particles. However, this requires a significant amount of future work.

Lysozyme was recovered from its aqueous solution by coprecipitation with sodium alginate. Electrostatic interaction between the two polyelectrolytes could occur between pH 2.0–9.0 and peaked at pH 3.0. The maximum lysozyme recovery of 97.10% was recorded at a mass ratio to sodium alginate of 2:1 and the presence of excessive sodium alginate reduced lysozyme precipitation. Complexation at pH 3.0 conferred the most compact and elastic network structure for the complex, but reduced the thermal stability and caused the greatest structural variation to lysozyme. The complexes separated at pH 4.5 and 6.0 could be dissolved by 1.0 mol/L NaCl, but that at pH 3.0 released only 77% lysozyme and further increase of NaCl concentration could not promote lysozyme liberation. It was concluded that coprecipitation with sodium alginate was potential in recovering lysozyme from its aqueous solutions and the dissociation of resultant complexes should be further enhanced to increase yield.

Lutein, abundant in dark leafy vegetables, has been associated with several health promoting effects. Still, to what extent different preparation conditions and practices affect the liberation of lutein from food is not fully understood. Here, we compared a range of domestic methods under realistic conditions to prepare spinach, the most common lutein-rich vegetable. After preparations, samples were processed by in vitro digestion and lutein was quantified by HPLC. Data indicate that short-term and medium-term heating of spinach, independent of heating method, substantially reduced liberated lutein and reduction was most pronounced after long boiling times. Interestingly, the loss of lutein in heated samples was partly compensated when samples were reheated in the microwave. However, the highest yield of liberated lutein was obtained from liquefied spinach. Additional dairy enhanced the liquefaction effect. Thus, for optimal liberation of lutein, liquefaction of raw spinach appears to be the method of choice.

The bioaccessibility of environmental contaminants has been assessed widely using in vitro simulation; however, the physiological parameters used vary greatly. In this study, we assessed the influence of various physiological parameters and food material on the oral or inhalation bioaccessibility of PM2.5-bound hydrophobic organic contaminants (HOCs), including halogenated flame retardants (HFRs), organophosphorus flame retardants (OPFRs), and polycyclic aromatic hydrocarbons (PAHs). The results showed that physiologically based pepsin and pancreatin have a small influence on the HOC liberation from particles. The bioaccessibility increased dramatically when the bile salt concentrations exceeding the critical micelle concentration, and application of porcine bile salts probably lead to underestimated bioaccessibility. Protein and carbohydrates significantly increased the bioaccessibility of most HOCs, while a significant bioaccessibility reduction was caused by green tea. The bioaccessibility of most HOCs was not promoted by liquor under normal physiological condition, but was significantly promoted under fast condition. Long residence time of PM2.5 in the lung (15 days) would result in higher mobilization of PAHs into the lung fluid than short time (one day). However, the inverse time-dependence for OPFRs suggests degradation in the lung fluid. A mechanism of hydrolysis of organophosphorus ester is hypothesized, and the half lives ranged from 17 to 90 days.

Triethanolamine (C6H15NO3, TEA) is one of the known organic amine accelerators for the cement-based materials. Triethanolamine hydrochloride (C6H15NO3·HCl, TEA·HCl), part of whose molecular structure is the same as TEA, can also be regarded as chloride. Thus the water requirement for the normal consistency, setting time, strength, hydration heat liberation, calcium hydroxide (CH) and ettringite (AFt) contents in the hardened paste with TEA·HCl were analyzed and the effect of TEA·HCl on the performance of cement paste was studied to assess the feasibility of TEA·HCl used as an identical accelerator. The results indicate that moderate TEA·HCl decreases the water requirement for the normal consistency and this decline is related to the formation of the absorbed film on the cement particle. Zeta electric potential result also proves the appearance of the absorbed film. It also shortens the setting times and alters strengths. But the alterations of setting times and strengths depend on the TEA·HCl content. Heat liberation result implies that it delays the end time of the induction period and also postpones tricalcium silicate (3CaO·SiO2, C3S) hydration at early age, however moderate TEA·HCl increases the rate of C3S hydration in accelerated phase. Excessive TEA·HCl accelerates the AFt conversion to monosulfoaluminate (AFm) after several hours. The conversion product is the AFm with 14 H2O. TEA·HCl changes the total heat liberation, and these pastes with more TEA·HCl liberate more heat before about 12 h, but this case is reverse after about 12 h. X-ray powder diffraction (XRD) and differential thermal analysis (DTA) results conformably confirm that excessive TEA·HCl delays C3S hydration and decreases CH content in the hardened paste, but it increases the AFt content in the hardened paste. Hardened pastes with TEA·HCl provide the higher content of AFt than the control even at 28d. Heat liberation, CH and AFt contents are closely responsible for the results of the setting times and strengths. These results will provide a reference for the TEA·HCl application as an accelerator in the practice.

Selecting the timing of laser treatment is an important task for improving O2-dependent photodynamic therapy (PDT) efficiency. Here, a black phosphorus-based strategy was developed for dual-mode monitoring oxygen self-supply, enhancing photodynamic therapy, and feeding back therapeutic effect. The hybridized nanoplatform (R-MnO2-FBP) was prepared by assembly of Rhodamine B (RhB)-encapsulated manganese dioxide (R-MnO2) as O2 supplier and indicator, and fluorescein isothiocyanate (FITC)-labelled peptide-functionalized black phosphorus as the theranostic agent. The time-dependent assays suggested that the O2 release was proportional to the liberation of Mn2+ and RhB in the R-MnO2-FBP system. After specific delivery into cancer cells, R-MnO2-FBP was dissociated in the acidic and H2O2-rich environment and generated oxygen to overcome hypoxia-associated PDT resistance. In the meantime, it released both Mn2+and RhB dye, leading to dual-mode (magnetic resonance imaging/fluorescence imaging) monitoring of the oxygen self-supply process. More significantly, the imaging-guided PDT in hypoxic cells displayed 51.6% of cell apoptosis at optimizing timing of laser application, which could also be confirmed by the FITC fluorescence recovery induced by the activated caspase-3 in apoptotic cells. In vivo photonic therapy by R-MnO2-FBP further demonstrated the ability of R-MnO2-FBP to choose the timing of laser application, providing an efficient approach for the enhancement of PDT process.

In order to achieve high-quality coal resources in western China, this study focused on a coal sample from the Shangwan Coal Mine, owned by the China Shendong Group, and employed scanning electron microscopy (SEM), mineral liberation analysis (MLA), and maceral component quantitative analysis for investigating the coal sample’s liberation characteristics and crack distribution patterns after pre-grading and microwave processing. The results show that the physical properties of coal maceral components significantly affected the related enrichment performances, and many intra-group and inter-group cracks were produced under the induction of microwave radiation. The cracks then developed and stopped growing among the different maceral components and mineral components, thereby inducing selective and random pulverization along the crack growth direction in further pulverization process and effectively enhancing the liberation properties of different components. Using the Sandbox method, the fractal dimension of the cracks on the particle surface was calculated to be 1.01, which confirmed the self-similarity of the cracks on the coal surface. Multi-intensification maceral liberation also yielded favorable grading performances. The inertinite content was the highest (75.23%) in grade-3 product, while the vitrinite content was the highest (66.3%) in grade-1 product; the corresponding enrichment ratios were 2.15 and 1.59, respectively. Moreover, the ash content in grade-2 product was the lowest, which dropped by 3.61% compared with that in raw coal sample.

The aims of this research were to obtain modified pectins of callus cultures using various culture conditions, to evaluate the relationship between the chemical characteristics of pectins, the swelling behavior and the release of prednisolone from calcium pectinate gel (CaPG) beads. An increase of the calcium concentration in the culture media correlated significantly with the rhamnogalacturonan I (RG-I) branching of the pectin. The beads from the pectin with a higher RG-I branching had the lower prednisolone release in a gastric fluid. The beads produced from the pectins obtained from callus cultured with a higher calcium concentration showed the lower prednisolone release. The swelling of the CaPG beads from pectin with a lower molecular weight (Mw) or linearity occurred to a lower degree. All beads prepared from modified pectins showed a high stability and a slow liberation of prednisolone in the simulated gastric and intestinal fluids, whereas rapid drug release in a colonic fluid. An applied strategy involving modification of the pectic structure using the abiotic factors allows obtaining the pectic gels with modified functional properties, in particular, with enhanced gastric and small intestinal resistance and a low drug release. These CaPG beads can be applied as the carriers for colon delivery of the drugs.

In this work, the flotation recoveries per size liberation class are modelled using the particle surface area. The resulting model presented a very good adjustment for recoveries per size with correlation factors above 0.9. In addition, once it is directly connected to particle characteristics, this model directly indicated the effect of particle size and liberation on flotation.

The influence of thermal shocks on the liberation characteristics of a by-product/discard from a coking coal preparation plant, known as coal middlings were investigated. The coal middlings are characterized by very high ash content (>45%), low carbon content (

Several studies have been developed to better understand the impact of froth on flotation recoveries. It has been shown that particle size and hydrophobicity affect froth stability. There are indications of selective attachment or detachment of particles depending on their characteristics. To evaluate the effect of froth height and recovery in a rougher stage, three continuous pilot flotation tests were performed with a chalcopyrite ore, each one with a specific froth height in the first rougher cell. Results were evaluated by global flows, by size fraction and by size-liberation classes. Liberation data were stereologically corrected and reconciled with process mass balance data using the beta adjustment method as described in the first paper of this series. In this second paper, different ways of expressing and analysing the recoveries per liberation classes provided an overview of the behaviour of particles in the process. Results show the trends presented by size liberation classes when the froth height increases and the recovery decreases. An empirical mathematical model was proposed to represent the recovery of liberation classes in size fractions.

G proteins play a central role in signal transduction and pharmacology. Signaling is initiated by cell-surface receptors, which promote GTP binding and the dissociation of Gα from the Gβγ subunits. Structural studies have revealed the molecular basis for subunit association with receptors, RGS proteins and downstream effectors. In contrast, the mechanism of subunit dissociation is poorly understood. We use cell signaling assays, MD simulations, biochemistry and structural analysis to identify a conserved network of amino acids that dictates subunit release. In the presence of the terminal phosphate of GTP, a glycine forms a polar network with an arginine and glutamate, putting torsional strain on the subunit binding interface. This “G-R-E motif” secures GTP and, through an allosteric link, discharges the Gβγ dimer. Replacement of network residues prevents subunit dissociation, regardless of agonist or GTP binding. These findings reveal the molecular basis for the final committed step of G protein activation.

The pro-metastatic potential of chemotherapy limits its therapeutic benefits against invasive cancer. Herein, a protein stabilized polymeric nanoparticle inspired relay drug delivery platform was developed to address post-chemotherapeutic metastasis. An ROS-responsive Phenylboronic acid (PBA)-Rich cationic polymer (RPP) bridges Doxorubicin (Dox) coordination and Snail-targeted siRNA (siSnail) compression, and natural apolipoprotein A-I (apoA-I) is attracted by surface electron-deficient PBA moieties for nanoparticle shaping, drug biostability, and tumour-penetration. The spatially-separated structure enables a timing-controlled relay drug delivery in tumour cells, where Dox gives a prior release phase by acidity, and RPP polymer is subsequently disintegrated by concentrated ROS for rapid siSnail liberation. In dual therapy, Dox pre-treatment upregulated pro-metastatic factors and aggravated metastasis, but subsequent liberation by siSnail silenced the central metastatic regulator of Epithelial-mesenchymal transition (EMT). The terminal nanoparticles exhibited advanced therapeutic efficacy, achieving primary tumour shrinkage (tumour weight inhibition, TWI of ~86.15%) and complete metastatic nodule elimination. This work promises to improve the clinical benefits of chemotherapy against invasive cancer.

In assessment of the volumetric liberation and surface exposure of ore particles, two-dimensional (2D) analysis, such as the widely used scanning electron microscope and energy dispersive X-ray (SEM/EDX)-based analysis, results in stereological bias with respect to the three-dimensional (3D) reality. Thus, a simulation-based stereological correction method for accurate assessment of volumetric liberation and surface exposure was developed. The method utilizes a pre-established database of numerically simulated binary particles to estimate 3D composition (or exposure) distributions only from measurable 2D composition (or exposure) distributions. Among the notable features of the method are the relatively small amount of 2D-distribution input data required, and the rapidity of the analysis. Experimental validation, and ex-post analysis of previously published research results, showed high estimation accuracy for various types of particles (including actual ore samples) examined in previous studies. In addition, the method is suitable for post analysis of SEM/EDX-based particle sectional liberation analysis.

The qualitative and quantitative profile of volatile compounds in agricultural distillate depends on numerous factors. Many such compounds, including higher alcohols, occur naturally, due to the metabolism of yeast during ethanol fermentation. Some are difficult to remove in the rectification process. For these reasons, it is desirable to reduce the synthesis of volatile compounds, among others higher alcohols, during the fermentation process. The results of the presented study showed that the raw materials, the method of starch liberation, and the initial pH of the sweet mashes affected the concentrations of higher alcohols in the distillates. Higher concentrations of 1-butanol, 1-propanol, and 2-propanol were found in distillates obtained from mashes prepared by the thermal-pressure method, while the remaining compounds occurred at higher concentrations in distillates obtained using the pressureless starch liberation method. The type of raw materials used had an influence on the concentration of the majority of higher alcohols. The content of 2-propanol, 2-methyl-1-propanol, 1-propanol, 1-butanol, 3-methyl-1-butanol, and 2-phenylethanol was lower in distillates obtained from mashes with an initial pH of 4, in comparison with those obtained from mashes with the pH set at 5.5.

Supramolecular host–guest complexes have the ability to prolong the circulation time, and promote the efficiency of hydrophobic drugs. Therefore, in this project we immobilized cyclodextrin (CD), as a host molecule for tamoxifen (TMX), to mitoxantrone (MTX) conjugated magnetic nanoparticles for simultaneous delivery of anti-cancer drugs toward folate-positive cancer cells. FESEM photography of the magnetic multi-drugs carrier confirmed a hollow circular structure for self-assembled layers of cyclodextrin conjugated to MNPs with average size about 95 nm. Drugs release from supramolecular magnetic nanoparticles (with 86.08% of TMX encapsulation and 60.3% of MTX loading) revealed that protease enzymes can enhance the MTX liberation at pH 5, but don't have any noticeable effect on liberation of TMX at both pH conditions. Also, the simultaneous presence of two drugs onto MNPs induced cytotoxicity in two cancer cell lines, MCF-7 and A549, which is different from the impact of each one of drugs alone. Therefore, we believe that this simultaneous carrier could enhance the efficiency of TMX and MTX anti-cancer drugs and be useful for the intended applications, due to hydrophilicity of supramolecular host–guest complexes and its inherent ability to target folate receptors, simultaneously.

A number of previous researchers have noticed that the degree of mineral liberation in a given size fraction is the same regardless of where in a comminution circuit a sample is collected. This behaviour has been observed for a range of ore types, and was found to be independent of the mode of breakage. This provides a useful heuristic for modelling the particle characteristics in mineral comminution and separation circuits. However, the published research does not explicitly consider the effect on the liberation behaviour of minerals of the amount of energy applied to break the ore. In this study, a gold-bearing pyrite ore and a copper sulphide ore were comminuted over a wide range of energy levels, using impact breakage. The liberation properties of the product particles were characterised using a Mineral Liberation Analyser (MLA). It was found that that the amount of impact energy applied did not significantly affect the degree of liberation of the minerals in a given size fraction, measured using particle sections. This provides sound experimental evidence to support the heuristic model.

PEGylated polylysine dendrimers have demonstrated potential as inhalable drug delivery systems that can improve the treatment of lung cancers. Their treatment potential may be enhanced by developing constructs that display prolonged lung retention, together with good systemic absorption, the capacity to passively target lung tumors from the blood and highly selective, yet rapid liberation in the tumor microenvironment. This study sought to characterize how the nature of cathepsin B–cleavable peptide linkers, used to conjugate doxorubicin (Dox) to a PEGylated (PEG570) G4 polylysine dendrimer, affects drug liberation kinetics and intravenous and pulmonary pharmacokinetics in rats. The construct bearing a self-emolative diglycolic acid-V-Citrulline linker exhibited faster Dox release kinetics compared to constructs bearing self-emolative diglycolic acid-glycine-leucine-phenylalanine-glycine (GLFG), or non-self-emolative glutaric acid-GLFG linkers. The V-Citrulline construct exhibited slower plasma clearance, but faster absorption from the lungs than a GLFG construct, although mucociliary clearance and urinary elimination were unchanged. Dox-conjugation enhanced localization in the bronchoalveolar lavage fluid compared to lung tissue, suggesting that projection of Dox from the dendrimer surface reduced tissue uptake. These data show that the linker chemistry employed to conjugate drugs to PEGylated carriers can affect drug release profiles and systemic and lung disposition.

Liberation is a key driver in all mineral separation processes as it limits the maximum possible grade for a given recovery. In flotation, this is further complicated by the fact that it is surface exposure of the floatable minerals that determines the ultimate performance. Liberation, grade and surface exposure are commonly quantified using Scanning Electron Microscopy coupled to Energy Dispersive X-ray spectroscopy (SEM/EDX) analysis of polished sections. The intrinsically 2D nature of this technique can result in significant sampling errors and stereological effects that can affect the quantification of the ore’s textural characteristics. X-ray microCT (XMT) is an imaging method that can non-invasively and non-destructively delineate ore fragments in 3D, thus providing an alternative method that eliminates the need for stereological corrections and readily provides surface exposure. A methodology and automated algorithm were developed for extracting this information from images of closely packed particles. By dividing these particles into classes based on both their surface exposure and grade, the extent to which there is preferential breakage of the particles can be assessed—an important consideration if sufficient surface liberation for good flotation performance is to be achieved at coarser particle sizes. Using low energy scanning simple 3D mineral maps can be obtained via XMT, allowing for the assessment of liberation and surface exposure for each mineral species. The methodology was tested on low grade porphyry copper ore as this is representative of the most commonly treated ore types for copper production.

Metastatic cancer is difficult to defeat with current treatments due to lack of etiological therapeutics and efficient delivery platforms. Employing tumor microenvironment in programming intelligent nanosystems has attracted considerable attention for combinative antitumor therapy. Herein, we proposed a core-shell based drug depot consisting of micellar core and crosslinked-gel shell for site-specific shuttling of paclitaxel (PTX) and KIAA1199 specific shRNA (shKIAA). Poly (e-caprolactone) were grafted with branched polyethylenimine (PEI-PCL) as micellar core, into which hydrophobic PTX was embedded; while shKIAA, a reliable RNAi regimen for metastatic cell inhibition was condensed with PEI through electrostatic interaction; and then photo-crosslinked hyaluronic acid (m-HA) was further coated as shell. The nanoscale drug depot shared HAase-triggered charge switching and desirable release profile. Upon reaching tumor region, HA shell was degraded by concentrated HAase, and facilitated drug shuttling to individual subcellular targeting site. Rapid intracellular trafficking of micellar core achieved endo/lysosomal escape and cytoplasmic liberation. The half-maximal inhibitory concentration (IC50) of “nanodepot” toward human breast cancer cell line MDA-MB-231 was 0.016 μg/mL (PTX concentration), approximately 3-fold decrease compared to that of monotherapy group (0.043 μg/mL). The tumor weight inhibition (TWI) is 83.30% in xenografted MDA-MB-231 tumor model and metastasis was effectively inhibited in 4T1 orthotopic tumors. Moreover, knockdown of KIAA1199 via sustainable RNAi affected a broad range of cellular functions including apoptosis, migration and invasion. Collectively, tumor environment differentiated spatiotemporal co-delivery fashion holds a great promise for combinative treatment with enhanced efficacy on metastatic cancer cases.

A methodology to characterize the mineral feed to the flotation process by liberation and particle size was proposed. This methodology considers a modification of the classical Gaudin liberation model, incorporating a grain size distribution for the mineral in the ore deposit. The results from a previous study were analyzed to test and validate the new methodology. The characterization of the mineral was successfully reproduced by liberation and particle size. At an industrial scale, a mineral in the rougher circuit feed of a copper flotation concentrator was characterized by liberation and particle size, applying the proposed methodology. From the above results, along with the overall recovery and top of froth (TOF) grade profiles, the characterization of the collection rate along the rougher circuit was performed. The rate constants and maximum recoveries were estimated by liberation and particle size. The results allowed the estimation of the mineral recovery profiles along the rougher flotation bank both by liberation and particle size classes.

5-Formyl-2-thiopheneboronic acid is a widely used building block for the synthesis of diverse structures, however, due to a significant instability its transformation to 5-arylthiophene-2-carboxaldehydes by C C couplings could be performed only in low yields. Herein, as a solution, a convenient technique is described for the preparation of 1,3-dioxolane-protected 5-arylthiophene-2-carboxaldehydes via a one-pot borylation–copper(I) chloride co-catalyzed Suzuki-Miyaura coupling reaction. The utilization of the in situ prepared 2-thiopheneboronic ester derivative is allowed by the method developed. Elimination of the crucial, acidic liberation step of boronic acid species resulted in improved yields and purities. In addition, comparison of various aryl bromides is shown to demonstrate the high tolerance of the transformation to functional groups.

This paper provides a further investigation of the role of vein structures in the ease of mineral liberation by random masking simulation of breakage. A copper porphyry ore with vein-type mineralisation underwent different methods of sample preparation for liberation analysis. A selected core was cut into semicircular slabs and another core underwent crushing. The slabs and the crushed particles were analysed in the MLA and subjected to simulated breakage from which the liberation of sulphides was determined. The result was linked with the liberation measured from particles of the same ore that have undergone actual breakage. The analysis further provided an indication of the significant contribution of veins in liberation. This information points out to a proper approach of texture and liberation analyses, and the better use of textural data from core scale logging relevant to mineral processing.

Within the scope of the evaluation and optimization of a grinding circuit, the breakage and mineral liberation characteristics of three low grade sulphide gold ore blends have been investigated by Bond tests, batch grinding tests, and mineral liberation characterization. The tests were conducted in a size range from 0.063 to 2 mm. It was found that the breakage of all blends follows a first-order behaviour for all feed sizes. The work index was correlated with the quartz content and the breakage rate deceleration parameter, which both showed a linear relationship. The correlation between breakage function fineness parameter and first-order rate constant also satisfied a linear relationship .The breakage parameters established from batch grinding and grindability studies indicate differences in the breakage behaviour of the three ore blends. However, the mineral liberation properties of the valuable phase in three blends show minor differences.

Gold nanoparticles (AuNPs) and matrix metalloproteinase (MMP)-2 cleavable peptides are clicked into gold nanoparticle clusters (AuNCs) for enhanced drug localization and micro computerized tomography (μCT) theranostic of tumors. AuNPs are co-functionalized with doxorubicin (DOX) and an azide-terminated polymer (DOX/N3@AuNPs), and the DOX/N3@AuNPs are associated into DOX@AuNCs in the presence of an alkyne-terminated MMP-2 cleavable peptide (alkyne-peptide-alkyne; APA) by click chemistry. MMP-2-dependent dissociation shows that DOX@AuNCs are highly sensitive to the MMP-2 and are almost completed digested into single nanoparticles. DOX liberation shows that > 75% of the conjugated DOX is bursted out from the digested DOX@AuNCs while < 20% of DOX is released from the integrate DOX@AuNCs within 3 h in acidic conditions, suggesting that DOX is only liberated from dissociated DOX@AuNCs in acidic conditions. In vivo study shows that DOX@AuNCs accumulate in tumor ~ 150 times higher than DOX/N3@AuNPs do and efficiently suppress tumor growth. Mice administered with AuNCs shows clearer μCT images of tumors. Thus, DOX@AuNCs are expected promising carriers for both anticancer therapy and tumor imaging.

Malonyl peroxides were used for the one-pot construction of hybrid structures by conjugation of heterocycle (3H-pyrazol-3-one, isoxazol-5(2H)-one, pyrazolidine-3,5-dione, or barbituric acid) and amine or alcohol. The first stage represents oxidative C–O coupling with liberation of the carboxyl group which is functionalized at the second stage thus affording ‘clicklike’ products with malonic linker.

The diversity of seven strains of Pseudomonas spp., isolated from raw milk, was studied for growth and proteolytic and lipolytic activity in milk at 4, 8 and 22 °C. Proteolysis was demonstrated by capillary electrophoresis (CE) and the liberation of free amino acids and free fatty acids were analysed by HPLC and GC, respectively. Activity varied considerably, according to strain, temperature and incubation time. After 9 days, proteolysis was demonstrated at 4 °C for several strains, but an increase in free amino acids was only notable at 22 °C. Lipolysis was most prominent at 22 °C although some activity was seen at 4 and 8 °C. All strains showing proteolytic activity were also lipolytic whereas two strains were only lipolytic. The results indicate that the strain of Pseudomonas and its properties determine the nature and seriousness of some of the deleterious changes that may occur in milk and milk products.

Lithium-ion Batteries (LIBs) have mostly replaced other types of batteries in numerous portable devices and electric vehicles due to their numerous advantages. With the continuous increase in the production of those batteries, the number of spent LIBs that have to be disposed of increases as well. Today, many recycling techniques are used for the spent LIBs, and a key problem is the liberation of metals from non-metals. This paper presents the liberation of electrode materials via attrition scrubbing, i.e. the separation of Al and Cu foil from graphite and LiCoO 2 particles, during which we have determined the influence of three independent variables — solid content, impeller speed and attrition time. To this purpose, the tests were carried out according to a central composite design. It showed that in the sample preparation phase, during comminution, 10% of graphite and LiCoO 2 particles separated by sieving (grain size – 0.1 mm) were recovered. The attrition scrubbing was carried out on the grain size of 8/0.1 mm. Results showed that, depending on the testing conditions, it was possible to recover from 49.52 to 82.30 % of graphite and LiCoO 2 particles. All three tested variables showed a significant influence on the attrition scrubbing process, while the impeller speed proved to have the strongest influence. Regarding the interaction of variables, the interaction of the attrition time and the solid content had the strongest influence, while other interactions were significantly less influential.

Drug-free antibacterial therapy, such as photodynamic therapy and chemodynamic therapy, has become a mainstream in the treatment of implant-associated infection (IAI) due to its considerable potential on effective eradication of pathogenic bacteria via yielding overwhelming reactive oxygen species (ROS). However, superfluous ROS after therapeutical process may elicit a detrimental effect on subsequent tissue regeneration. To address this tough issue, we innovatively devise a photo-activated copper ferrite (CuFe2O4) heterojunction coating on bioinert polyetheretherketone (PEEK) implant through hydrothermal treatment and π-π-π stacking. The heterojunction coatings not only generate localized hyperthermia and ROS upon 808 nm NIR illumination, but also trigger Fenton(-like) reaction and glutathione (GSH) depletion in bacterial infectious microenvironment (IME), all leading to robust and cyclic antibacterial property through synergistic photothermal/photodynamic/chemodynamic therapy. Besides, the decorated implants are demonstrated to show superior cytocompatibility and osteogenic-promoting capability. The mice subcutaneous implantation further confirms the excellent in vivo photo-disinfection. The advantage of the heterojunction coatings lies on its enhancement in tissue generation and osteogenesis after antibacterial dynamic therapy because the liberation of micronutrient element (Cu, Fe) is significantly augmented exposed to NIR light, showing photo-enhanced osteogenicity. As envisaged, this work provides a new strategy to empower PEEK implants with an integrative feature of bacteriostasis and osteogenicity to combat intractable IAI through synergistic photo/Fenton-therapy.

The aim of this study was to investigate the in vivo and in vitro effects of dietary ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) and their derivatives on the expression of TP53 and their relationship with cellular proliferation and death in a murine mammary adenocarcinoma model. BALB/c mice were divided in three diet groups: chia oil (ChO) rich in ω-3, corn oil (CO) rich in ω-6/ω-3 and safflower oil (SO) rich in ω-6 and subcutaneously inoculated with LMM3 mammary tumor cell line. Results demonstrated that diets with higher concentration of omega-6 PUFAs induced an increment of linoleic and arachidonic acid on tumor cell membranes increasing ROS liberation, 12(S)-HHT generation, TP53, Ki67 expression and cell proliferation. However, diets enriched with high content in omega-3 PUFAs induced higher tumor cell apoptosis and tumor infiltration of CD3+ lymphocytes, lowest cell viability and proliferation. Dietary omega-3 PUFAs nutritional intervention can be used as a potential preventative strategy to inhibit the molecular signaling pathways involved in the mammary tumor growth process as the TP53.

The heuristic of a constant liberation by size independent of the degree of comminution has been established as a robust assumption over time. Therefore, when assessing the comminution circuit performance, achieving a final target P80 size at the lowest possible energy and cost seems to be the only concern. The introduction of higher capacity fine screening to replace hydrocyclones challenges this fixed approach due to the inherent difference in classification principles between the technologies. The impact of classification efficiency and mode on the liberation properties of a polymetallic ore ground in a production ball mill circuit are presented. It was found that the liberation properties remained constant across the comminution device but were significantly different across the circuit. The circuit closed with screens was found to improve the coarse particle liberation in comparison to the hydrocyclones. The liberation data is presented and implications for circuit performance are discussed. It is postulated that the assessment of comminution circuit design and performance should be based on the ultimate objective, recovery of the valuable minerals, and thus be based on the ore- and process-specific recovery window, not on a fixed ‘grind size’.

The objectives of this study were to evaluate, in vitro and in vivo, the contribution of muscarinic receptors to the effects of Ruscus extract. Ruscus extract was tested in competition binding experiments at recombinant human muscarinic receptors, heterologous expressed in Chinese Hamster Ovary (CHO) cells and in cellular assays measuring Ca2+ liberation and activator protein-1 (AP-1) reporter gene activation. The impact of muscarinic blockade on prolonged treatment outcome was evaluated using the hamster cheek pouch (HCP) microcirculation examining macromolecular permeability increase induced by histamine or ischemia/reperfusion (I/R), mean arteriolar and venular diameters, functional capillary density and I/R-induced leukocyte rolling and sticking. Ruscus extract exhibited affinities for muscarinic receptor subtypes at a range of 50-100μg/ml and behaved as partial agonist at human recombinant M1 and M3 receptors for Ca2+ liberation, confirmed in an AP-1 reporter gene assay. In the HCP model, topical application of atropine completely or partially blocked Ruscus extract-induced reductions of histamine- and I/R-induced increases of macromolecular permeability and leukocyte-endothelium interaction. Our results showed that Ruscus extract in vitro binds and activates different subtypes of muscarinic receptors and in vivo its anti-inflammatory effects are, at least partially, mediated via muscarinic receptors.

The enzyme phospholipase A2 (PLA2) is overexpressed in the inflamed intestine in inflammatory bowel disease (IBD) patients, and in this work we aimed to exploit PLA2 as a prodrug-activating enzyme for a novel PL-drug conjugate, thereby liberating the free drug specifically in the targeted diseased tissue(s). The proposed prodrug contains a drug moiety covalently bound through a linker to the sn-2 position of a phospholipid (PL). The NSAID diclofenac was used as model molecule, and four different linker lengths (2, 4, 6 and 8 -CH2 units) were studied. The four PL-diclofenac conjugates were synthesized and characterized by LC/MS and NMR. PLA2-mediated activation of the prodrugs was analyzed in-vitro, and the remaining intact complex and free drug liberation were assessed after incubation with PLA2. The rate and degree of PLA2-mediated activation were highly dependent on the linker length; 2- and 4-carbon linker conjugates were activated to lower extent than the 6-carbon conjugate, and longer linker again decreased the affinity towards PLA2. The 6-carbon linker conjugate was found to be the optimal and released ~95% of the free drug after incubation with PLA2, whereas only ~20% were delivered by the 2-carbon linker prodrug. The 6-carbon linker conjugate was shown to be stable in intestinal perfusate, fresh plasma, and pH4.0 and 6.8 buffers, but not at pH1.0. In conclusion, the results of this work confirm the feasibility of our general aim to exploit PLA2 as a prodrug-activating enzyme of PL-drug conjugates. This may provide a novel oral drug targeting approach in IBD therapy.

The relationship between shear force and selective liberation of middling coking coal was investigated by crushing the coal at different shear angles (15°, 30°, 45°, 60°, and 75°). Subsequent analysis of the middling coking coal revealed that as the ash content of coal increased, the shear strength and cohesion increased, while the internal friction angle gradually decreased. Increasing the shear angle caused a gradual increase in the quantity of coarse particles and a decrease in the quantity of fine particles, ultimately leading to a dominant particle size of > 10 mm at a shear angle of 75°. The cumulative ash and cumulative yield curves showed that the liberation of middling coking coal through crushing was optimum when the shear angle was smaller than the internal friction angle. Lamellar tear fractures observed with low-shear-angle crushing could contribute to the liberation of coal, but the step-like morphology characteristics of medium and high shear angles was not conducive to liberation. Because the liberation of middling coking coal through crushing was optimum when the shear angle was smaller than the internal friction angle, a high ash content or high shear angle may make the release of clean coal more difficult.

The mammalian nuclear division cycle is coordinated with nuclear envelope breakdown (NEBD), in which the entire nuclear envelope (NE) is dissolved to allow chromosomes to access their segregation vehicle, the spindle. In other eukaryotes, complete NEBD is replaced by localized disassembly or remodeling of the NE. Although the molecular mechanisms controlling NE disassembly are incompletely understood, coordinated cycles of modification of specific NE components drive breakdown. Here, we review the current state of knowledge regarding NE disassembly and argue for a role of chromosome-NE contacts in triggering initiation of NE disassembly and thereby, cell division.

The synthesis of novel amphiphilic poly(propylene sulfide) (PPS) and poly( N -isopropylacrylamide) (PNIPAm) block copolymers is reported as a strategy to respond stimuli in inflammatory tissues. In addition to the formation of defined PPS- block -PNIPAm assemblies, the encapsulation of fluorescent dyes and the selective response to the heat and oxidants are studied. The synthesis of the dual responsive PPS-b-PNIPAm is carried out by combining a living anionic ring-opening and an atom transfer radical polymerization (ATRP) process. The resulting copolymers are self-assembled in water to form aggregated structures, which are characterized by dynamic light scattering (DLS) and scanning electronic microscopy (SEM). DLS measurements show that heat and oxidants cause a significant change to the hydrodynamic diameter of the particles. Fluorescent spectroscopy data confirms the liberation of the encapsulated dye, which indicates the decomposition of the particles and validates the concept of stimuli-triggered payload release. Finally, cytotoxicity assays confirm that the PPS-b-PNIPAm copolymer is biocompatible with A549 lung cancer cells.

This paper describes the role of vein structures to better understand and interpret the origin of mineral liberation based on random masking simulation. An HQ half core from a copper porphyry deposit was selected and was cut into semicircular slabs of 1 cm thickness. Selected slabs were polished for MLA analysis. Classified MLA images were then subjected to image processing to identify and separate the veins from the disseminated grains. Random masking was applied on the images to simulate breakage and generate progeny particles from which liberation of sulphides was determined. Results of the simulation provided an indication of the contribution of veins in the liberation of minerals at coarser size and the increased degree of liberation. The work in this paper also suggests cutting drill cores and using slabs for texture analysis provides more intact textural features of the ore both at micro and mesoscale. Particularly, if veins occur to some extent, cutting the drill core into slabs is more suitable to preserve this structure providing a better understanding of the origin of mineral liberation.

International audience; This study presents an evaluation of an innovative technique for the treatment of concrete waste by electrical fragmentation. Scientific arguments are made, indicating that it is possible to strive for the recovery of waste by jointly recycling aggregates and the hydrated cement paste, in order to manufacture new concrete of the same mechanical quality as that produced using raw materials. The results of electrical fragmentation tests on concrete show that i) fragmentation level and selectivity are significantly enhanced when the size of the constituent aggregate in the concrete increases, which is a positive result because the largest proportion of most concrete mixes comprises coarse aggregate (45% of 5/20 mm aggregate); ii) the mineralogical nature of the aggregate has little impact on the electrical fragmentation level and has none on its selectivity, which are positive results demonstrating the robustness of the process in terms of its ability to process aggregate of different origins and iii) aggregate liberation degree depends on neither the energy level applied to the concrete, nor the quality of the process water, which are positive results for industrial applications. The results of this study show that electrical fragmentation has potential for integration as part of a recycling process for concrete waste on an industrial scale.