Selective Uptake Research Articles

Engineered Antibody Fragment against the Urokinase Plasminogen Activator for Fast Delineation of Triple-Negative Breast Cancer by Positron Emission Tomography.

The urokinase plasminogen activator (uPA) and its cofactors are important regulators of tumor initiation and progression (including metastasis), and its overexpression is associated with unfavorable situations in cancer patients. We have previously used positron emission tomography (PET) imaging with a radiolabeled monoclonal antibody against the uPA (named ATN-291) to detect the uPA signaling activity in various cancer types; however, good tumor contrast can only be observed 24 h postinjection. To shorten the antibody circulation time and decrease interactions of ATN-291 with the mononuclear phagocyte system (MPS), our goal in this study is to develop an engineered antibody fragment (F(ab')2) from the parent antibody. By pepsin digestion and chromatography purification, ATN-291 F(ab')2 was obtained and characterized. Subsequently, it was conjugated with NOTA-Bn-NCS or fluorescein isothiocyanate (FITC) for PET imaging and fluorescence-mediated cellular analysis (i.e., flow cytometry or fluorescence microscopy). We confirmed that ATN-291 F(ab')2 still maintained a good targeting efficacy for the uPA in MDA-MB-231 cells (uPA+) and it had a faster blood clearance speed compared with ATN-291, while its interaction with MPS has been significantly decreased. In rodent tumor xenografts, radiolabeled ATN-291 F(ab')2 had a selective and persistent uptake in MDA-MB-231 tumors, with an early tumor-to-blood ratio of 1.3 ± 0.8 (n = 4) at 2 h postinjection from PET imaging. During our observation, radiolabeled ATN-291 F(ab')2 was excreted from both renal and hepatobiliary pathways. Radiolabeled ATN-291 F(ab')2 was also used for detecting uPA fluctuation during the tumor treatment in test animals. We concluded that radiolabeled ATN-291 F(ab')2 could be used as fast as PET cancer diagnostics with versatile applicability.

Loudness Dependence of Auditory-evoked Potentials, a Marker of Central Serotonergic Activity, is Affected by Fasting and Selective Uptake of Food.

Serotonin is an important neuromodulator involved in many physiological processes including mood and satiety. In the brain, serotonin is manufactured from tryptophan, as serotonin itself cannot cross the blood-brain barrier. Previous research has shown that blood-tryptophan levels increase upon ingestion of carbohydrates and decrease upon protein consumption. How this translates into serotonin availability is as yet under-researched. Therefore, we examined the effect of fasting versus consuming carbohydrates or protein on central serotonergic activity using a repeated-measures crossover design in a sample of 37 healthy men. The loudness dependence of auditory-evoked potentials (LDAEP) serves as a noninvasive method to study central serotonergic activity. Blood-glucose levels and mood changes were also monitored before and after the nutritional intervention. The intervention had a significant nutrition-specific effect on LDAEP and blood-glucose levels. A significant difference emerged between the fasting condition and satiety, with LDAEP being lower during satiety, irrespective of the type of food. Thus, this indicator of serotonergic activity increased after food consumption, which was further related to mood improvement. Moreover, the LDAEP differed between the 2 measurements only for the carbohydrate testing day, suggesting that LDAEP can be selectively modulated by the type of nutrition consumed. Our data further indicate a high intraindividual stability of LDAEP, as the electrophysiological signals were very similar in the fasting condition across the 2 testing days. Together, these findings demonstrate that the LDAEP can serve as a biological marker for central serotonergic activity, while at the same time being sensitive to nutritional changes.

The organometallic ferrocene exhibits amplified anti-tumor activity by targeted delivery via highly selective ligands to αvβ3, αvβ6, or α5β1 integrins

High levels of reactive oxygen species (ROS) in tumors have been shown to exert anti-tumor activity, leading to the concept of ROS induction as therapeutic strategy. The organometallic compound ferrocene (Fc) generates ROS through a reversible one-electron oxidation. Incorporation of Fc into a tumor-targeting, bioactive molecule can enhance its therapeutic activity and enable tumor specific delivery. Therefore, we conjugated Fc to five synthetic, Arg-Gly-Asp (RGD)-based integrin binding ligands to enable targeting of the cell adhesion and signaling receptor integrin subtypes αvβ3, α5β1, or αvβ6, which are overexpressed in various, distinct tumors. We designed and synthesized a library of integrin-ligand-ferrocene (ILF) derivatives and showed that ILF conjugates maintained the high integrin affinity and selectivity of their parent ligands. A thorough biological characterization allowed us to identify the two most promising ligands, an αvβ3 (L2b) and an αvβ6 (L3b) targeting ILF, which displayed selective integrin-dependent cell uptake and pronounced ferrocene-mediated anti-tumor effects in vitro, along with increased ROS production and DNA damage. Hence, ILFs are promising candidates for the selective, tumor-targeted delivery of ferrocene to maximize its anti-cancer efficacy and minimize systemic toxicity, thereby improving the therapeutic window of ferrocene compared to currently used non-selective anti-cancer drugs.

Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis.

Aims Fibroblast growth factor (FGF) 21, a key regulator of energy metabolism, is currently evaluated in humans for treatment of type 2 diabetes and non-alcoholic steatohepatitis. However, the effects of FGF21 on cardiovascular benefit, particularly on lipoprotein metabolism in relation to atherogenesis, remain elusive.Methods and results Here, the role of FGF21 in lipoprotein metabolism in relation to atherosclerosis development was investigated by pharmacological administration of a half-life extended recombinant FGF21 protein to hypercholesterolaemic APOE*3-Leiden.CETP mice, a well-established model mimicking atherosclerosis initiation and development in humans. FGF21 reduced plasma total cholesterol, explained by a reduction in non-HDL-cholesterol. Mechanistically, FGF21 promoted brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning, thereby enhancing the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT and into browned WAT, consequently accelerating the clearance of the cholesterol-enriched remnants by the liver. In addition, FGF21 reduced body fat, ameliorated glucose tolerance and markedly reduced hepatic steatosis, related to up-regulated hepatic expression of genes involved in fatty acid oxidation and increased hepatic VLDL-triglyceride secretion. Ultimately, FGF21 largely decreased atherosclerotic lesion area, which was mainly explained by the reduction in non-HDL-cholesterol as shown by linear regression analysis, decreased lesion severity, and increased atherosclerotic plaque stability index.Conclusion FGF21 improves hypercholesterolaemia by accelerating triglyceride-rich lipoprotein turnover as a result of activating BAT and browning of WAT, thereby reducing atherosclerotic lesion severity and increasing atherosclerotic lesion stability index. We have thus provided additional support for the clinical use of FGF21 in the treatment of atherosclerotic cardiovascular disease.

Lipidated Peptidomimetic Ligand-Functionalized HER2 Targeted Liposome as Nano-Carrier Designed for Doxorubicin Delivery in Cancer Therapy.

The therapeutic index of chemotherapeutic agents can be improved by the use of nano-carrier-mediated chemotherapeutic delivery. Ligand-targeted drug delivery can be used to achieve selective and specific delivery of chemotherapeutic agents to cancer cells. In this study, we prepared a peptidomimetic conjugate (SA-5)-tagged doxorubicin (Dox) incorporated liposome (LP) formulation (SA-5-Dox-LP) to evaluate the targeted delivery potential of SA-5 in human epidermal growth factor receptor-2 (HER2) overexpressed non-small-cell lung cancer (NSCLC) and breast cancer cell lines. The liposome was prepared using thin lipid film hydration and was characterized for particle size, encapsulation efficiency, cell viability, and targeted cellular uptake. In vivo evaluation of the liposomal formulation was performed in a mice model of NSCLC. The cell viability studies revealed that targeted SA-5-Dox-LP showed better antiproliferative activity than non-targeted Dox liposomes (Dox-LP). HER2-targeted liposome delivery showed selective cellular uptake compared to non-targeted liposomes on cancer cells. In vitro drug release studies indicated that Dox was released slowly from the formulations over 24 h, and there was no difference in Dox release between Dox-LP formulation and SA-5-Dox-LP formulation. In vivo studies in an NSCLC model of mice indicated that SA-5-Dox-LP could reduce the lung tumors significantly compared to vehicle control and Dox. In conclusion, this study demonstrated that the SA-5-Dox-LP liposome has the potential to increase therapeutic efficiency and targeted delivery of Dox in HER2 overexpressing cancer.

Targeted delivery of protein arginine deiminase-4 inhibitors to limit arterial intimal NETosis and preserve endothelial integrity.

Recent evidence suggests that 'vulnerable plaques', which have received intense attention as underlying mechanism of acute coronary syndromes over the decades, actually rarely rupture and cause clinical events. Superficial plaque erosion has emerged as a growing cause of residual thrombotic complications of atherosclerosis in an era of increased preventive measures including lipid lowering, antihypertensive therapy, and smoking cessation. The mechanisms of plaque erosion remain poorly understood, and we currently lack validated effective diagnostics or therapeutics for superficial erosion. Eroded plaques have a rich extracellular matrix, an intact fibrous cap, sparse lipid, and few mononuclear cells, but do harbour neutrophil extracellular traps (NETs). We recently reported that NETs amplify and propagate the endothelial damage at the site of arterial lesions that recapitulate superficial erosion in mice. We showed that genetic loss of protein arginine deiminase (PAD)-4 function inhibited NETosis and preserved endothelial integrity. The current study used systemic administration of targeted nanoparticles to deliver an agent that limits NETs formation to probe mechanisms of and demonstrate a novel therapeutic approach to plaque erosion that limits endothelial damage. We developed Collagen IV-targeted nanoparticles (Col IV NP) to deliver PAD4 inhibitors selectively to regions of endothelial cell sloughing and collagen IV-rich basement membrane exposure. We assessed the binding capability of the targeting ligand in vitro and evaluated Col IV NP targeting to areas of denuded endothelium in vivo in a mouse preparation that recapitulates features of superficial erosion. Delivery of the PAD4 inhibitor GSK484 reduced NET accumulation at sites of intimal injury and preserved endothelial continuity. NPs directed to Col IV show selective uptake and delivery of their payload to experimentally eroded regions, illustrating their translational potential. Our results further support the role of PAD4 and NETs in superficial erosion.

EQCM sensor for targeting psychoactive drug via rationally designed molecularly imprinted polymeric nanoparticles (nanoMIPs)

Molecularly imprinted polymers (MIPs) having the potential to mimic the selectivity and sensitivity of biological molecular recognition are blended here with piezoelectric transducer (EQCM) able to provide ‘real time’ monitoring of molecular level events with extreme sensitivity. In this work, molecularly imprinted polymer nanoparticles selective for a psychoactive drug, cathinone were synthesized, characterized and applied for specific and selective uptake in water. Nanoparticles were separated by centrifugation and characterized for their size and zeta potential. p-Phenylene diamine was chosen as functional monomer to imprint S-cathinone via in silico studies. Molecularly imprinted nanoparticles were eletrodeposited on gold coated quartz crystal electrode of electrochemical quartz crystal microbalance (EQCM). Molecular imprinting experiments were optimized for selective and specific uptake of S-cathinone. Thus fabricated EQCM sensor was able to discriminate between stereoisomers and other close structural analogues also. Imprinting data were successfully fitted to Freundlich adsorption isotherm and curves for non-imprinted and imprinted data were compared. Under optimized conditions, response of nanoMIP-EQCM sensor is linearly proportional to S-cathinone concentration with detection limit as 0.12 ng mL−1 and quantification limit as 0.409 ng mL−1 and imprinting factor as 8. Hence, a highly specific and selective nanoMIP-EQCM sensor is fabricated in a facile manner.

Thermal Decomposition Behavior of Prussian Blue in Various Conditions.

Prussian blue analogs (PBA) are widely studied for radioactive cesium decontamination. However, there are fewer works related to their post use storage. Considering the oxidative stabilization of the material after the selective uptake of Cs, the thermogravimetric properties in powder and bead form, with various Cs and other alkali metal ions adsorbed, and various heating rates were studied. TG-DTA taken in dry air condition shows an exothermic decomposition at ~270 °C. This temperature varied with the heating rate, mass, and the proportion of adsorbed ions. The best condition for complete oxidation of Prussian blue (PB) is found to be a gradual oxidative decomposition by heating in the temperature range of 200–220 °C until the total mass is decreased by >35%. After this, the temperature could be safely increased to >300 °C for the complete oxidative decomposition of PB that formed iron oxide and salt of the adsorbed Cs. A pilot scale test conducted using the radioactive Cs adsorbed Prussian blue microbeads (PB-b) confirmed that no Cs was released in the effluent air during the process.

A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis.

Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans.

Discovery of 6-substituted thieno[2,3-d]pyrimidine analogs as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis in folate receptor expressing human tumors

We discovered 6-substituted thieno[2,3-d]pyrimidine compounds (3–9) with 3–4 bridge carbons and side-chain thiophene or furan rings for dual targeting one-carbon (C1) metabolism in folate receptor- (FR) expressing cancers. Synthesis involved nine steps starting from the bromo-aryl carboxylate. From patterns of growth inhibition toward Chinese hamster ovary cells expressing FRα or FRβ, the proton-coupled folate transporter or reduced folate carrier, specificity for uptake by FRs was confirmed. Anti-proliferative activities were demonstrated toward FRα-expressing KB tumor cells and NCI-IGROV1 ovarian cancer cells. Inhibition of de novo purine biosynthesis at both 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase and glycinamide ribonucleotide formyltransferase (GARFTase) was confirmed by metabolite rescue, metabolomics and enzyme assays. X-ray crystallographic structures were obtained with compounds 3–5 and human GARFTase. Our studies identify first-in-class C1 inhibitors with selective uptake by FRs and dual inhibition of enzyme targets in de novo purine biosynthesis, resulting in anti-tumor activity. This series affords an exciting new platform for selective multi-targeted anti-tumor agents.

Thiosemicarbazide-modified/ion-imprinted phenolic resin for selective uptake of cadmium ions

Cd(II)-imprinted Cd(II) resin obtained from a thiosemicarbazide derivative of salicylic acid was prepared and evaluated for selective uptake of Cd(II) ions. In the beginning, the thiosemicarbazide derivative of salicylic acid (H2TCS) was developed as a functional ligand that was then coordinated with Cd(II) ions to obtain the Cd-complex [CdTCS(H2O)3]. After the full investigation of the ligand and its complex, they copolymerized with resorcinol in presence of formalin, and the obtained resinous material was eluted with 0.1 M HNO3 solution to extract the polymer incorporated Cd(II) ions and finally produce the Cd(II) ions selective Cd-RTCS sorbent. The maximum cadmium ions capacity by the Cd-RTCS reached 164 ± 1 mg/g, which could be a relatively high and promising value. Also, the adsorption isotherms were interpreted better with the Langmuir model. In addition, the Cd(II) sorption using Cd-RTCS was tested in a competitive medium of Pb(II), Ni(II), Zn(II), and, Cu(II) ions and the results indicated a considerable selectivity toward the Cd(II) ions over the coexisted metals.

Targeting macrophage liver X receptors by hydrogel-encapsulated T0901317 reduces atherosclerosis without effect on hepatic lipogenesis.

Targeting macrophage but not hepatocyte liver X receptors (LXRs) can reduce atherosclerosis without effect on hepatic lipogenesis. In this study, we encapsulated LXR ligands with D-Nap-GFFY to form a nanofibre hydrogel (D-Nap-GFFY-T0901317 or GFFY-T0901317) and determined its effect on atherosclerosis, hepatic lipogenesis and the underlying mechanisms involved. D-Nap-GFFY-T0901317 was subcutaneously injected to proatherogenic diet-fed apoE-deficient (Apoe-/- ) mice, followed by determination of the development of atherosclerosis, liver steatosis and the involved mechanisms, with comparison of T0901317 oral administration. Subcutaneous injection of D-Nap-GFFY-T0901317 to Apoe-/- mice inhibited atherosclerosis at a comparable level as T0901317 oral administration without effect on hepatic lipogenesis. More importantly, D-Nap-GFFY-T0901317 regressed the advanced lesions. In arterial wall, D-Nap-GFFY-T0901317 reduced macrophage/foam cells, necrotic cores and calcification and increased collagen content. It activated expression of ABCA1/G1 and smooth muscle α-actin, while inhibiting expression of intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1). D-Nap-GFFY-T0901317 also reduced serum pro-inflammatory cytokines and facilitated Kupffer cell M2 polarization. Mechanistically, D-Nap-GFFY-T0901317 was selectively taken up by macrophages but not hepatocytes, resulting in activation of macrophage ABCA1/G1 expression, while having no effect on lipogenic genes in hepatocytes. Moreover, the selective uptake of D-Nap-GFFY-T0901317 by macrophages was mainly completed in a scavenger receptor class A-dependent manner. Our study demonstrates that D-Nap-GFFY-T0901317 reduces atherosclerosis without effect on hepatic lipogenesis by targeting macrophage LXRs selectively, indicating its potential application for atherosclerosis treatment.

Transient Lipid-Protein Structures and Selective Ganglioside Uptake During α-Synuclein-Lipid Co-aggregation.

α-Synuclein is a membrane-interacting protein involved in Parkinson’s disease. Here we have investigated the co-association of α-synuclein and lipids from ganglioside-containing model membranes. Our study relies on the reported importance of ganglioside lipids, which are found in high amounts in neurons and exosomes, on cell-to-cell prion-like transmission of misfolded α-synuclein. Samples taken along various stages of the aggregation process were imaged using cryogenic transmission electron microscopy, and the composition of samples corresponding to the final state analyzed using NMR spectroscopy. The combined data shows that α-synuclein co-assembles with lipids from the ganglioside (GM1)-containing model membranes. The lipid-protein samples observed during the aggregation process contain non-vesicular objects not present at the final stage, thus capturing the co-existence of species under non-equilibrium conditions. A range of different lipid-protein co-assemblies are observed during the time course of the reaction and some of these appear to be transient assemblies that evolve into other co-aggregates over time. At the end of the aggregation reaction, the samples become more homogeneous, showing thin fibrillar structures heavily decorated with small vesicles. From the NMR analysis, we conclude that the ratio of GM1 to phosphatidyl choline (PC) in the supernatant of the co-aggregated samples is significantly reduced compared to the GM1/PC ratio of the lipid dispersion from which these samples were derived. Taken together, this indicates a selective uptake of GM1 into the fibrillar aggregates and removal of GM1-rich objects from the solution.

Pinwheel-Shaped Tetranuclear Organoboron Catalysts for Perfectly Alternating Copolymerization of CO2 and Epichlorohydrin.

The copolymerization of carbon dioxide (CO2) and epoxides to produce aliphatic polycarbonates is a burgeoning technology for the large-scale utilization of CO2 and degradable polymeric materials. Even with the wealth of advancements achieved over the past 50 years on this green technology, many challenges remain, including the use of metal-containing catalysts for polymerization, the removal of the chromatic metal residue after polymerization, and the limited practicable epoxides, especially for those containing electron-withdrawing groups. Herein, we provide kinds of pinwheel-shaped tetranuclear organoboron catalysts for epichlorohydrin/CO2 copolymerization with >99% polymer selectivity and quantitative CO2 uptake (>99% carbonate linkages) under mild conditions (25-40 °C, 25 bar of CO2). The produced poly(chloropropylene carbonate) has the highest molecular weight of 36.5 kg/mol and glass transition temperature of 45.4 °C reported to date. The energy difference (ΔEa = 60.7 kJ/mol) between the cyclic carbonate and polycarbonate sheds light on the robust performance of our metal-free catalyst. Control experiments and density functional theory (DFT) calculations revealed a cyclically sequential copolymerization mechanism. The metal-free feature, high catalytic performance under mild conditions, and no trouble with chromaticity for the produced polymers imply that our catalysts are practical candidates to advance the CO2-based polycarbonates.

In Vitro and In Vivo Efficacy of a Novel Glucose-Methotrexate Conjugate in Targeted Cancer Treatment.

Methotrexate (MTX) is a commonly used antimetabolite, which inhibits folate and DNA synthesis to be effective in the treatment of various malignancies. However, MTX therapy is hindered by the lack of target tumor selectivity. We have designed, synthesized and evaluated a novel glucose–methotrexate conjugate (GLU–MTX) both in vitro and in vivo, in which a cleavable linkage allows intracellular MTX release after selective uptake through glucose transporter−1 (GLUT1). GLU–MTX inhibited the growth of colorectal (DLD-1), breast (MCF-7) and lung (A427) adenocarcinomas, squamous cell carcinoma (SCC-25), osteosarcoma (MG63) cell lines, but not in WI-38 healthy fibroblasts. In tumor cells, GLU–MTX uptake increased 17-fold compared to unconjugated MTX. 4,6-O-ethylidene-α-D-glucose (EDG), a GLUT1 inhibitor, significantly interfered with GLU–MTX induced growth inhibition, suggesting a glucose-mediated drug uptake. Glu-MTX also caused significant tumor growth delay in vivo in breast cancer-bearing mice. These results show that our GLUT-MTX conjugate can be selectively uptake by a range of tumor cells to cause their significant growth inhibition in vitro, which was also confirmed in a breast cancer model in vivo. GLUT1 inhibitor EDG interfered with these effects verifying the selective drug uptake. Accordingly, GLU–MTX offers a considerable tumor selectivity and may offer cancer growth inhibition at reduced toxicity.

Unmodified Titanium Dioxide Nanoparticles as a Potential Contrast Agent in Photon Emission Computed Tomography

Highly crystalline titanium dioxide nanoparticles (TiO2-NPs) are synthesized via a simple hydrothermal technique. After structural and compositional analysis, the as-synthesized unmodified TiO2-NPs are tested for improvement in two modes of kilovoltage radiation therapy and single-photon emission computed tomography (SPECT)/computed tomography (CT). Our results show that the unmodified TiO2-NPs provide an observable enhancement in CT scan image contrast ranging from 0 ± 3 HU (without NPs) to 283.7 ± 3 HU (0.23 g/mL). TiO2-NPs has excellent biocompatibility, selective uptake at target sites, and reduced toxicity. The unmodified TiO2-NPs as a contrast agent can significantly improve the existing methods of diagnosing and treating cancer.

Removal performance and mechanism of anti-eutrophication anions of phosphate by CaFe layered double hydroxides

Wastewater from industries can contain excessive phosphate anions to cause eutrophication of lakes and rivers. The calcium iron-based layered double hydroxides (CaFe-LDHs) can improve immobilization the migration of phosphate anions in anti-eutrophication. In this study, we developed an efficient structure for the selective uptake of phosphate anions in aqueous solution on CaFe-LDHs. We also discuss removal mechanism of anions by the CaFe-LDHs related with structure modulation variation that happens during calcination process.

A Batch Experiment of Cesium Uptake Using Illitic Clays with Different Degrees of Crystallinity

Radiocesium released by the severe nuclear accident and nuclear weapon test is a hazardous material. Illitic clays play a key role in the spatial distribution of radiocesium in groundwater environments due to selective uptake sites at the illite mineral, such as frayed edge sites. However, the cesium uptake capabilities of illitic clays are diverse, which could be associated with the illite crystallinity. This study was performed to determine the cesium uptake of illitic clays and evaluate the crystallinity effects on cesium uptake using statistical approaches. A total of 10 illitic clays showed various crystallinity, which was parameterized by the full width at half maximum (FWHM) at 10 Å XRD peak ranging from 0.15 to 0.64. The uptake behavior of illitic clays was well fitted with the Freundlich model (i.e., r2 > 0.946). The uptake efficiency of illitic clays increased with the decrease in dissolved cesium concentrations. The cesium uptake was significantly correlated with the FWHM and cation exchange capacity, suggesting that the uptake becomes higher with decreasing crystallinity through expansion of the edge site and/or formation of ion-exchangeable sites.

Synergistic material and process development: Application of a metal-organic framework, Cu-TDPAT, in single-cycle hydrogen purification and CO2 capture from synthesis gas

We employ a synergistic material and process development strategy to improve the performance of a single-cycle vacuum pressure swing adsorption (VPSA) process for the hydrogen purification and the CO2 separation from reforming-based hydrogen synthesis. Based on process-informed adsorbent selection criteria, including high CO2 cyclic capacity and selective uptake of impurities like CO, N2, and CH4 over H2, a metal organic framework (MOF), Cu-TDPAT, is selected. First, adsorption isotherms of CO2, CO, CH4, N2 and H2 are measured. Subsequently, a column model is used for optimization-based analysis of the VPSA cycle with Cu-TDPAT as the adsorbent to assess both the separation performance, and the process performance in terms of energy consumption and productivity. The adsorption characteristics of Cu-TDPAT require an adaptation of the original VPSA process to increase the CO2 separation performance of the process. After this adaptation, Cu-TDPAT clearly outperforms the benchmark material, zeolite 13X, in several metrics including higher H2 purities and recoveries and fewer columns needed for a continuous separation process. Most importantly, Cu-TDPAT offers a two-fold improvement in CO2 productivities when compared to zeolite 13X, thus substantially decreasing the bed size required to achieve the same throughput. However, zeolite 13X remains the better adsorbent for reaching high CO2 purities and recoveries due to its higher selectivity for CO2 over all other components in the gas stream, which leads to an overall lower energy consumption. The obtained results show that the final performance strongly depends on an interplay of various factors related to both material and process. Hence, an integrated process and material design approach should be the new paradigm for developing novel gas separation processes.

Neutrophil-to-hepatocyte communication via LDLR-dependent miR-223-enriched extracellular vesicle transfer ameliorates nonalcoholic steatohepatitis.

Neutrophil infiltration around lipotoxic hepatocytes is a hallmark of nonalcoholic steatohepatitis (NASH); however, how these 2 types of cells communicate remains obscure. We have previously demonstrated that neutrophil-specific microRNA-223 (miR-223) is elevated in hepatocytes to limit NASH progression in obese mice. Here, we demonstrated that this elevation of miR-223 in hepatocytes was due to preferential uptake of miR-223-enriched extracellular vesicles (EVs) derived from neutrophils as well other types of cells, albeit to a lesser extent. This selective uptake was dependent on the expression of low-density lipoprotein receptor (LDLR) on hepatocytes and apolipoprotein E (APOE) on neutrophil-derived EVs, which was enhanced by free fatty acids. Once internalized by hepatocytes, the EV-derived miR-223 acted to inhibit hepatic inflammatory and fibrogenic gene expression. In the absence of this LDLR- and APOE-dependent uptake of miR-223-enriched EVs, the progression of steatosis to NASH was accelerated. In contrast, augmentation of this transfer by treatment with an inhibitor of proprotein convertase subtilisin/kexin type 9, a drug used to lower blood cholesterol by upregulating LDLR, ameliorated NASH in mice. This specific role of LDLR and APOE in the selective control of miR-223-enriched EV transfer from neutrophils to hepatocytes may serve as a potential therapeutic target for NASH.