ABSTRACT
Yes-associated protein (YAP) is a key oncogene in the Hippo tumor suppression pathway, historically challenging to target due to its intrinsically disordered nature. Leveraging recent advances in high-throughput screening that identified several YAP binders, we employed proteolysis-targeting chimera technology to develop a series of YAP degraders. Utilizing NSC682769, a known YAP binder, linked with VHL ligand 2 or pomalidomide via diverse linkers, we synthesized degraders including YZ-6. This degrader not only recruits the E3 ligase VHL for the rapid and sustained degradation of YAP but also effectively inhibits its nuclear localization, curtailing YAP/TEAD-mediated transcription in cancer cell lines such as NCI-H226 and Huh7. This dual action significantly diminishes YAP's oncogenic activity, contributing to the potent antiproliferative effects observed both in vitro and in a Huh7 xenograft mouse model. These results underscore the potential of PROTAC-mediated YAP degradation as a strategy for treating YAP-driven cancers.
ABSTRACT
To explore green gold leaching reagents, a series of imidazolium cyanate ionic liquids (ILs), 1-ethyl-3-methyl-imidazolium cyanate ([C2MIM][OCN]), 1-propyl-3-methyl-imidazolium cyanate ([C3MIM][OCN]) and 1-butyl-3-methyl-imidazolcyanate ([C4MIM][OCN]) were synthesized and characterized by Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR) and thermogravimetric (TG) analysis. In this research, the imidazolium cyanates were utilized as a solute, which not only decreased the usage of ILs but also increased their gold dissolution capability. The gold dissolution performances of three imidazolium cyanates were characterized by dynamic leaching test and Scanning Electron Microscopy (SEM). The results show that the all three imidazolium cyanates had a gold dissolution ability, and the shorter the carbon chain on the imidazole ring in imidazolium cyanate, the faster the gold dissolution rate. The gold dissolution performance of [C2MIM][OCN] was the best, and the weight loss of gold leaf was 2.9 mg/cm2 at 40 °C after 120 h dissolution in [C2MIM][OCN] mixed with 10 wt. % water. Besides this, the gold dissolution rate increased with the increase in the concentration of imidazolium cyanates as well as the reaction temperature. The gold dissolution performances of imidazolium cyanates in different solvents including water, acetonitrile, dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) were also investigated, and the weaker the polarity of the solvent, the more conducive it was to the gold dissolution reaction. The mechanism of gold dissolution by imidazolium cyanates was investigated through NMR spectroscopy and Electrospray Ionization Mass Spectrometry (ESI-MS). It was inferred that during the process of gold dissolution, Au was oxidized to Au+ and the imidazolium cations were deprotonated to form N-heterocyclic carbenes, which coordinated with gold to form gold complexes and achieve gold dissolution.
ABSTRACT
For over two hundred years, cyanide has served as the primary reagent for gold extraction. However, due to its high toxicity, the use of cyanide poses significant risks. Traditional low-toxicity leaching reagents have limitations that restrict their widespread industrial application, leading to the necessity for the development of new, efficient, and low-toxic gold leaching reagents to support sustainable gold production. In this study, a novel, efficient, and low-toxicity gold extraction reagent was synthesized at high temperatures by combining urea, sodium carbonate, and a specific iron salt. The research delved into the leaching ability of the reagent under different synthesis conditions and examined the generation of free cyanide content as a by-product. Findings indicated that reagents synthesized with either potassium ferrocyanide or potassium ferricyanide displayed comparable leaching capabilities. Reagents synthesized at 800 °C exhibited lower levels of free cyanide ions and reduced toxicity. Additionally, this reagent demonstrated exceptional selectivity for gold, while in minimal dissolution of copper, iron, nickel, lead, and iron from computer central processing unit (CPU) pins. Under optimal conditions, the efficiency of gold extraction from CPU pins reached 94.65%. Hence, this reagent holds significant potential for the low-toxicity extraction of gold from electronic waste or auriferous concentrates.
Subject(s)
Electronic Waste , Gold , Indicators and Reagents , Temperature , Cyanides , Iron , CopperABSTRACT
Hydrogen bonds play an important role in the interaction between surfactants. In this study, the effect of three different ethoxylated alcohols (OP-10, NP-10, AEO-9) on the collecting behavior of sodium oleate (NaOL) in the flotation of quartz was investigated. To explore the mechanism, the hydrogen bond between ethoxylated alcohols and NaOL was analyzed using molecular dynamics (MD) simulation. The results showed that ethoxylated alcohols promoted the collecting performance of NaOL and reduced the dosage of the activator CaO and the collector NaOL in the flotation of quartz. The Zeta potential measurement illustrated that ethoxylated alcohols promoted the adsorption of OL- on the activated quartz surface and the degree of promotion was in the order of OP-10 > NP-10 > AEO-9. The MD simulation results showed that a hydrogen bond presented between ethoxylated alcohols and OL-. Due to the hydrogen bond between the ethoxylated alcohols and OL-, the attraction force between OL- and the quartz surface increased with the addition of ethoxylated alcohols in the order of OP-10 > NP-10 > AEO-9 based on the MD simulation results. As the result, the addition of ethoxylated alcohols increased the adsorption density of OL- on the activated quartz surface, which explained the promotion of the collecting performance of OL- in the flotation of quartz.
ABSTRACT
For effective removal and utilization of fluorine resources from industrial wastewater, stepwise removal and recovery of fluorine were accomplished by seeding crystallization and flotation. The effects of seedings on the growth and morphology of CaF2 crystals were investigated by comparing the processes of chemical precipitation and seeding crystallization. The morphologies of the precipitates were analyzed by X-ray diffraction (XRD) and scanning electron microscope (SEM) measurements. The seed crystal, fluorite, helps improve the growth of perfect CaF2 crystals. The solution and interfacial behaviors of the ions were calculated by molecular simulations. The existing perfect surface of fluorite was proven to provide the active sites for ion adhesion and formed a more ordered attachment layer than the precipitation procedure. The precipitates were then floated to recover calcium fluoride. By stepwise seeding crystallization and flotation, the products with a CaF2 purity of 64.42% can be used to replace parts of metallurgical-grade fluorite. Both removal of fluorine from wastewater and the reutilization of the fluorine resource were realized.
Subject(s)
Fluorine , Wastewater , Crystallization , X-Ray Diffraction , Computer SimulationABSTRACT
Liver fibrosis is a common outcome of most chronic liver insults/injuries that can develop into an irreversible process of cirrhosis and, eventually, liver cancer. In recent years, there has been significant progress in basic and clinical research on liver cancer, leading to the identification of various signaling pathways involved in tumorigenesis and disease progression. Slit glycoprotein (SLIT)1, SLIT2, and SLIT3 are secreted members of a protein family that accelerate positional interactions between cells and their environment during development. These proteins signal through Roundabout receptor (ROBO) receptors (ROBO1, ROBO2, ROBO3, and ROBO4) to achieve their cellular effects. The SLIT and ROBO signaling pathway acts as a neural targeting factor regulating axon guidance, neuronal migration, and axonal remnants in the nervous system. Recent findings suggest that various tumor cells differ in SLIT/ROBO signaling levels and show varying degrees of expression patterns during tumor angiogenesis, cell invasion, metastasis, and infiltration. Emerging roles of the SLIT and ROBO axon-guidance molecules have been discovered in liver fibrosis and cancer development. Herein, we examined the expression patterns of SLIT and ROBO proteins in normal adult livers and two types of liver cancers: hepatocellular carcinoma and cholangiocarcinoma. This review also summarizes the potential therapeutics of this pathway for anti-fibrosis and anti-cancer drug development.
Subject(s)
Liver Neoplasms , Receptors, Immunologic , Adult , Humans , Receptors, Immunologic/genetics , Receptors, Immunologic/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Glycoproteins/metabolism , Liver Cirrhosis , Liver Neoplasms/genetics , Receptors, Cell Surface/metabolismABSTRACT
Gold leaching is an important process to extract gold from ore. Conventional alkaline cyanide process and alternative nontoxic lixiviants including thiosulfate, thiourea, thiocyanate, and halogen have been widely investigated. However, density functional theory (DFT) study on the gold complexes Au(CN)2-, Au(S2O3)23-, Au[SC(NH2)2]2+, Au(SCN)2-, and AuCl2- required for discovering and designing new highly efficient and environmentally friendly gold leaching reagents is lacking, which is expected to support constructive information for the discovery and designation of new high-efficiency and environmentally friendly gold leaching reagents. In this study, the structure information, electron-transferring properties, orbital interaction, and chemical bond composition for complexes Au(CN)2-, Au(S2O3)23-, Au[SC(NH2)2]2+, Au(SCN)2-, and AuCl2- depending on charge decomposition analysis (CDA), natural bond orbital (NBO), natural resonance theory (NRT), electron localization function (ELF), and energy decomposition analysis (EDA) were performed based on DFT calculation. The results indicate that there is not only σ-donation from ligand to Au+, but also electron backdonation from Au+ to ligands, which strengthens the coordinate bond between them. Compared with Cl-, ligands CN-, S2O32-, SC(NH2)2, and SCN- have very large covalent contribution to the coordinate bond with Au+, which explains the special stability of Au-CN and Au-S bonds. The degree of covalency and bond energy in Au-ligand bonding decreases from Au(CN)2-, Au(S2O3)23-, Au[SC(NH2)2]2+, Au(SCN)2-, to AuCl2-, which interprets the stability of the five complexes: Au(CN)2- > Au(S2O3)23- > Au[SC(NH2)2]2+ > Au(SCN)2- > AuCl2-.
ABSTRACT
Liver fibrosis is the common outcome of many chronic liver diseases, resulting from altered cell-cell and cell-matrix interactions that promote hepatic stellate cell (HSC) activation and excessive matrix production. This study aimed to investigate functions of cellular communication network factor 2 (CCN2)/Connective tissue growth factor (CTGF), an extracellular signaling modulator of the CYR61/CTGF/Nov (CCN) family, in liver fibrosis. Tamoxifen-inducible conditional knockouts in mice and hepatocyte-specific deletion of this gene in rats were generated using the Cre-lox system. These animals were subjected to peri-central hepatocyte damage caused by carbon tetrachloride. Potential crosstalk of this molecule with a new profibrotic pathway mediated by the Slit2 ligand and Roundabout (Robo) receptors was also examined. We found that Ccn2/Ctgf was highly upregulated in periportal hepatocytes during carbon tetrachloride-induced hepatocyte damage, liver fibrosis and cirrhosis in mice and rats. Overexpression of this molecule was observed in human hepatocellular carcinoma (HCC) that were surrounded with fibrotic cords. Deletion of the Ccn2/Ctgf gene significantly reduced expression of fibrosis-related genes including Slit2, a smooth muscle actin (SMA) and Collagen type I during carbon tetrachloride-induced liver fibrosis in mice and rats. In addition, Ccn2/Ctgf and its truncated mutant carrying the first three domains were able to interact with the 7th -9th epidermal growth factor (EGF) repeats and the C-terminal cysteine knot (CT) motif of Slit2 protein in cultured HSC and fibrotic murine livers. Ectopic expression of Ccn2/Ctgf protein upregulated Slit2, promoted HSC activation, and potentiated fibrotic responses following chronic intoxication by carbon tetrachloride. Moreover, Ccn2/Ctgf and Slit2 synergistically enhanced activation of phosphatidylinositol 3-kinase (PI3K) and AKT in primary HSC, whereas soluble Robo1-Fc chimera protein could inhibit these activities. These observations demonstrate conserved cross-species functions of Ccn2/Ctgf protein in rodent livers. This protein can be induced in hepatocytes and contribute to liver fibrosis. Its novel connection with the Slit2/Robo signaling may have therapeutic implications against fibrosis in chronic liver disease.
ABSTRACT
Yes-associated protein (YAP), a central effector in the Hippo pathway, is involved in the regulation of organ size, stem cell self-renewal, and tissue regeneration. In this study, we observed YAP activation in patients with alcoholic steatosis, hepatitis, and cirrhosis. Accumulation of this protein in the nucleus was also observed in murine livers that were damaged after chronic-plus-single binge or moderate ethanol ingestion combined with carbon tetrachloride intoxication (ethanol/CCl4 ). To understand the role of this transcriptional coactivator in alcohol-related liver injury, we knocked out the Yap1 gene in hepatocytes of floxed homozygotes through adeno-associated virus (AAV8)-mediated deletion utilizing Cre recombinase. Yap1 hepatocyte-specific knockouts (KO) exhibited hemorrhage, massive hepatic necrosis, enhanced oxidative stress, elevated hypoxia, and extensive infiltration of CD11b+ inflammatory cells into hepatic microenvironments rich for connective tissue growth factor (Ctgf) during ethanol/CCl4 -induced liver damage. Analysis of whole-genome transcriptomics indicated upregulation of genes involved in hypoxia and extracellular matrix (ECM) remodeling, whereas genes related to hepatocyte proliferation, progenitor cell activation, and ethanol detoxification were downregulated in the damaged livers of Yap1 KO. Acetaldehyde dehydrogenase (Aldh)1a1, a gene that encodes a detoxification enzyme for aldehyde substrates, was identified as a potential YAP target because this gene could be transcriptionally activated by a hyperactive YAP mutant. The ectopic expression of the human ALDH1A1 gene caused increase in hepatocyte proliferation and decrease in hepatic necrosis, oxidative stress, ECM remodeling, and inflammation during ethanol/CCl4 -induced liver damage. Taken together, these observations indicated that YAP was crucial for liver repair during alcohol-associated injury. Its regulation of ALDH1A1 represents a new link in liver regeneration and detoxification.
Subject(s)
Aldehyde Dehydrogenase 1 Family/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Ethanol/toxicity , Liver Regeneration , Retinal Dehydrogenase/metabolism , YAP-Signaling Proteins/physiology , Aldehyde Dehydrogenase 1 Family/genetics , Animals , Cell Proliferation , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Female , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Retinal Dehydrogenase/genetics , Signal TransductionABSTRACT
In this study, the effect of surfactants and electrolytes on stability of kaolinite dispersions was analyzed by measuring suspension transmittance, zeta potential, and adsorption. It was experimentally found that the compression of kaolinite electric double layer caused by NaCl addition may reduce the electrostatic repulse force to facilitate the aggregation of kaolinite particles. Surfactant facilitate the aggregation of kaolinite particles mainly through the adsorption of it on the surface of kaolinite to generate hydrophobic force. Compared to anionic surfactant, the cationic surfactant has a better flocculation effect because it can be used in a wide pH range and its adsorption can reduce the electrostatic repulse force between kaolinite particles.
Subject(s)
Electrolytes/chemistry , Kaolin/chemistry , Static Electricity , Surface-Active Agents/chemistry , Water/chemistry , Flocculation , Hydrogen-Ion ConcentrationABSTRACT
Recycling precious metals from secondary resources is of great environmental and economic significance. In this study, the Zr-based MOFs UiO-66-NH2 was synthesized and used to adsorb Au (III) in aqueous solution. The ultrafine particle size (â¼50 nm), excellent crystallinity and huge specific surface area (1039.2 m2 ·g-1) were verified by transmission electron microscope (TEM), powder X-ray diffraction (PXRD) and surface area analysis. About 50 % Au (III) was adsorbed within 6 min and the maximum adsorption capacity at 298 K reached up to 650 mg·g-1, showing superiority to traditional adsorbents. The general order kinetics model and Liu equation were suitable to describe the adsorption process, which was spontaneous, endothermic and driven by the increasing system entropy. Electrostatic attraction between -NH3+ and Au (III) anions and inner complexation to Zr-OH played a vital role in adsorption. Au (â ¢) was reduced to Au° by amino groups via redox reaction certified by X-ray photoelectron spectroscopy (XPS), PXRD and high-resolution transmission electron microscopy (HRTEM) analysis. Moreover, UiO-66-NH2 displayed high selectivity, robust stability and excellent reusability, making it an ideal candidate for gold recycling in industrial practice.
ABSTRACT
The roles of cationic and anionic surfactants in assembling reduced graphene oxide hydrogels (RGOHs) and controlling their porous structures are studied in this work. The mechanisms of the surfactant effects were studied by x-ray diffraction, Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy, and electrochemical methods. The morphology and structure of graphene oxide and RGOH were examined by atomic force microscopy, scanning electron microscopy, and transmission electron microscopy. The experimental results showed that surfactants could modify the structure of as-prepared RGOH but did not change the chemical or physical properties of the reduced graphene oxide (RGO) sheets. The modification was achieved by changing the orientation of graphene oxide sheets in aqueous solutions. It was also found that RGOH could not be prepared in the presence of high dosages of cationic surfactant because the RGO sheets were stacked piecewise with just one orientation and could not be cross-linked at any angle. The presence of an anionic surfactant did not affect the formation of RGOH but only enlarged the pores in its cross-linking structure. In addition, RGOHs prepared with anionic surfactants were found to have a higher specific capacitance compared to RGOHs prepared with cationic surfactants.
ABSTRACT
In this paper, the mechanism of enhanced membrane separation by ultrasound is analyzed. The main factors affecting the separation of enhanced membrane by ultrasonic technology is studied, the application and research progress of ultrasonic technology in membrane separation are studied. The conclusion are (a) cavitation caused by ultrasonic radiation is the main factor that increases the permeation flux of dextran solution (b) higher intensity of sound is helpful to the cleaning of the film; (c) ultrasound enhancement is related to temperature and operating pressure; (d) the film assembly shell material also affect the ultrasonic effect. In addition, the influence of ultrasonic wave on membrane structure is also discussed. Result indicates that the membrane separation process under the action of ultrasound does improve its permeability, but sometimes ultrasound can also cause damage to the membrane. Application of ultrasonic techniques for enhancing the separation process of membrane is also reviewed.
ABSTRACT
The dispersion behavior of particles is of great significance in selective flocculation flotation. The interfacial interaction between coal and the main impurity mineral (kaolinite) particles with the effect of an anionic polyacrylamide (PAM A401) was explored by the extended Derjaginâ»Landauâ»Verweyâ»Overbeek (DLVO) theory. The involved surface free energy components of fine mineral particles were estimated using the van Oss-Chaudhury-Good theory and Washburn equation. After adsorption of PAM A401, the range and absolute value of the hydrophobic interaction VHA of the coal particles decreased, the electrostatic repulsive potential increased, and the total potential energy changed from -1.66 × 105 to -4.03 × 104 kT at the separation distance of 5 nm. For interactions between the kaolinite and coal particles after PAM A401 adsorption, the electrostatic repulsive potential increased and the hydrophilic repulsive potential energy decreased. The energy barrier at the separation distance of 0.2 nm decreased from 2.78 × 104 to 2.29 × 104 kT. The total potential energy between the kaolinite and coal particles after PAM A401 adsorption was still repulsive, and the range of the repulsive interaction increased from ~0.05 to 47 nm to ~0.05 to 50 nm. The total potential energy of the coal particles after PAM A401 adsorption was still attractive. This behavior of coal and kaolinite particles with the effect of PAM A401 indicates the possibility of enhanced fine coal separation by the method of selective flocculation flotation.
ABSTRACT
A series of Fe/CeO2-intercalated clay catalysts were synthesized successfully, the physicochemical properties of the catalysts were characterized by XRD, BET, XRF, TG, FT-IR, O2-TPD, H2-TPR and XPS methods. The catalytic performances for selective catalytic oxidation of H2S were further investigated, all catalysts exhibited high catalytic activities. Among them 5% Fe/Ce-Lap presented the best activity at 180 degreeC and the maximum sulfur yield was up to 96% due to the interaction between iron and cerium, which improved the redox ability of Fe3+ . Moreover, the strong oxygen adsorption capacity and the well dispersion of iron species improved the catalytic performance efficiently.
Subject(s)
Aluminum Silicates/chemistry , Cerium/chemistry , Hydrogen Sulfide/chemistry , Intercalating Agents/chemistry , Iron/chemistry , Silicates/chemistry , Adsorption , Catalysis , Clay , Oxidation-ReductionABSTRACT
Hydrotalcite-based MgAl mixed oxides were synthesized by urea hydrolysis and constant-pH coprecipitation methods, and characterized by means of X-ray diffraction (XRD) , thermal gravity analysis-differential thermal gravity (TG-DTG) , scanning electron microscope (SEM), N2-adsorption/desorption and CO2 temperature programmed desorption (CO2-TPD), and their adsorption performances for SO2 were also tested. It was found that MgAl mixed oxides prepared by coprecipitation method would facilitate the catalyst to maintain a high specific area (148. 1 m2.g-1) and more basic sites, which resulted in higher SO2 adsorption capacity and velocity. The SO2 adsorption capacity of the mixed oxides prepared by urea hydrolysis and constant-pH coprecipitation methods were 0.55 g.g-1and 0. 79 gg-1 respectively at 700 degreeC.
Subject(s)
Aluminum Hydroxide/chemistry , Magnesium Hydroxide/chemistry , Oxides/chemistry , Sulfur Dioxide/chemistry , Adsorption , Catalysis , Hydrogen-Ion Concentration , Hydrolysis , Temperature , Urea/chemistry , X-Ray DiffractionABSTRACT
The low recovery of pertussis toxin (PT) and the low resolving efficiency of chromatography, due to the instability of PT in low salt condition, are the main challenges for its purification. We aplied 2 mol/L urea to prevent the aggregation and disassociation of PT during the purification by ion-exchange chromatography (IEC) and gel filtration chromatography (GFC). The effect of urea on the purification of PT was studied by ELISA assay and non-reduced SDS-PAGE. The activity recoveries of PT and filamentous hemagglutinin (FHA) in IEC and GFC, the resolution efficiency in GFC and the purities of PT and FHA were improved obviously by adding 2 mol/L urea in the mobile phase. The results highlight the potential application of urea in the acellular pertussis vaccine (APV) manufacture procedure.