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1.
Adv Healthc Mater ; 12(13): e2202830, 2023 05.
Article in English | MEDLINE | ID: mdl-36716704

ABSTRACT

Recent preclinical and clinical studies have highlighted the improved outcomes of combination radiotherapy and immunotherapy. Concurrently, the development of high-Z metallic nanoparticles as radiation dose enhancers has been explored to widen the therapeutic window of radiotherapy and potentially enhance immune activation. In this study, folate-modified hafnium-based metal-organic frameworks (HfMOF-PEG-FA) are evaluated in combination with imiquimod, a TLR7 agonist, as a well-defined interferon regulatory factor (IRF) stimulator for local antitumor immunotherapy. The enhancement of radiation dose deposition by HfMOF-PEG-FA and subsequent generation of reactive oxygen species (ROS) deregulates cell proliferation and increases apoptosis. HfMOF-PEG-FA loaded with imiquimod (HfMOF-PEG-FA@IMQ) increases DNA double-strand breaks and cell death, including apoptosis, necrosis, and calreticulin exposure, in response to X-ray irradiation. Treatment with this multipronged therapy promotes IRF stimulation for subsequent interferon production within tumor cells themselves. The novel observation is reported that HfMOF itself increases TLR7 expression, unexpectedly pairing immune agonist and receptor upregulation in a tumor intrinsic manner, and supporting the synergistic effect observed with the γH2AX assay. T-cell analysis of CT26 tumors following intratumoral administration of HfMOF-PEG-FA@IMQ with radiotherapy reveals a promising antitumor response, characterized by an increase in CD8+ and proliferative T cells.


Subject(s)
Interferon Type I , Metal-Organic Frameworks , Neoplasms , Humans , Imiquimod/pharmacology , Toll-Like Receptor 7/agonists , Metal-Organic Frameworks/pharmacology , Hafnium/metabolism , Up-Regulation , Interferon Type I/pharmacology , Neoplasms/drug therapy , Neoplasms/radiotherapy , Cell Line, Tumor
2.
ACS Appl Mater Interfaces ; 13(42): 50132-50140, 2021 Oct 27.
Article in English | MEDLINE | ID: mdl-34662123

ABSTRACT

The simulation of human brain neurons by synaptic devices could be an effective strategy to break through the notorious "von Neumann Bottleneck" and "Memory Wall". Herein, opto-electronic synapses based on layered hafnium disulfide (HfS2) transistors have been investigated. The basic functions of biological synapses are realized and optimized by modifying pulsed light conditions. Furthermore, 2 × 2 pixel imaging chips have also been developed. Two-pixel visual information is illuminated on diagonal pixels of the imaging array by applying light pulses (λ = 405 nm) with different pulse frequencies, mimicking short-term memory and long-term memory characteristics of the human vision system. In addition, an optically/electrically driven neuromorphic computation is demonstrated by machine learning to classify hand-written numbers with an accuracy of about 88.5%. This work will be an important step toward an artificial neural network comprising neuromorphic vision sensing and training functions.


Subject(s)
Biomimetic Materials/metabolism , Disulfides/metabolism , Hafnium/metabolism , Neural Networks, Computer , Synapses/metabolism , Biomimetic Materials/chemical synthesis , Biomimetic Materials/chemistry , Disulfides/chemical synthesis , Disulfides/chemistry , Hafnium/chemistry , Humans , Light , Machine Learning , Materials Testing , Synapses/chemistry
3.
Microsc Res Tech ; 74(9): 825-30, 2011 Sep.
Article in English | MEDLINE | ID: mdl-23939670

ABSTRACT

This ultrastructural study showed that nonisotopic methanolic hafnium chloride and aqueous lead solution was an excellent new electron stain for enhancing TEM contrasts of fungal and plant cell structures. The ultrastructural definition provided by the new stain was often superior to that provided by conventional staining with uranyl acetate and lead. Definition of fine ultrastructure was also supported by quantitative data on TEM contrast ratios of organelles and components in fungal and plant cells. In particular, polysaccharides, which were localized in cell walls, glycogen particles, starch grains, and plant Golgi vesicle components, were much more reactive to the new stain than to the conventional one. The new nonisotopic stain is useful for enhancing the contrast of ultrastructure in biological tissues and is a safer alternative to uranyl acetate.


Subject(s)
Fungi/ultrastructure , Hafnium/metabolism , Microscopy, Electron/methods , Plant Cells/ultrastructure , Staining and Labeling/methods , Lead/metabolism , Methanol/metabolism , Organelles/ultrastructure , Organometallic Compounds/metabolism
4.
Biol Trace Elem Res ; 103(1): 69-82, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15695849

ABSTRACT

We investigated the uptake of inorganic elements (Be, Na, Mg, K, Ca, Sc, Mn, Co, Zn, Se, Rb, Sr, Y, Zr, Ce, Pm, Gd, and Hf) and the effect of Ca on their uptake in carrots (Daucus carota cv. U.S. harumakigosun) by the radioactive multitracer technique. The experimental results suggested that Na, Mg, K, and Rb competed for the functional groups outside the cells in roots with Ca but not for the transporter-binding sites on the plasma membrane of the root cortex cells. In contrast, Y, Ce, Pm, and Gd competed with Ca for the transporters on the plasma membrane. The selectivity, which was defined as the value obtained by dividing the concentration ratio of an elemental pair, K/Na, Rb/Na, Be/Sr, and Mg/Sr, in the presence of 0.2 and 2 ppm Ca by that of the corresponding elemental pair in the absence of Ca in the solution was estimated. The selectivity of K and Rb in roots was increased in the presence of Ca. The selectivity of Be in roots was not affected, whereas the selectivity of Mg was increased by Ca. These observations suggest that the presence of Ca in the uptake solution enhances the selectivity in the uptake of metabolically important elements against unwanted elements.


Subject(s)
Calcium/pharmacology , Daucus carota/metabolism , Metals, Alkaline Earth/metabolism , Metals, Rare Earth/metabolism , Beryllium/metabolism , Calcium/metabolism , Cerium/metabolism , Cobalt/metabolism , Daucus carota/drug effects , Gadolinium/metabolism , Hafnium/metabolism , Magnesium/metabolism , Manganese/metabolism , Plant Roots/drug effects , Plant Roots/metabolism , Plant Shoots/drug effects , Plant Shoots/metabolism , Plutonium/metabolism , Potassium/metabolism , Radioisotopes , Rubidium/metabolism , Scandium/metabolism , Selenium/metabolism , Sodium/metabolism , Stimulation, Chemical , Strontium/metabolism , Yttrium/metabolism , Zinc/metabolism , Zirconium/metabolism
5.
Nat Struct Biol ; 10(4): 297-302, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12598891

ABSTRACT

Transferrins transport Fe3+ and other metal ions in mononuclear-binding sites. We present the first evidence that a member of the transferrin superfamily is able to recognize multi-nuclear oxo-metal clusters, small mineral fragments that are the most abundant forms of many metals in the environment. We show that the ferric ion-binding protein from Neisseria gonorrhoeae (nFbp) readily binds clusters of Fe3+, Ti4+, Zr4+ or Hf4+ in solution. The 1.7 A resolution crystal structure of Hf-nFbp reveals three distinct types of clusters in an open, positively charged cleft between two hinged protein domains. A di-tyrosyl cluster nucleation motif (Tyr195-Tyr196) is situated at the bottom of this cleft and binds either a trinuclear oxo-Hf cluster, which is capped by phosphate, or a pentanuclear cluster, which in turn can be capped with phosphate. This first high-resolution structure of a protein-mineral interface suggests a novel metal-uptake mechanism and provides a model for protein-mediated mineralization/dissimilation, which plays a critical role in geochemical processes.


Subject(s)
Bacterial Proteins , Cation Transport Proteins/chemistry , Cation Transport Proteins/metabolism , Metals/metabolism , Animals , Biological Transport, Active , Crystallography, X-Ray , Hafnium/metabolism , Iron/metabolism , Models, Biological , Models, Molecular , Molecular Structure , Neisseria gonorrhoeae/metabolism , Protein Conformation , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism
6.
J Anim Sci ; 80(12): 3307-14, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12542172

ABSTRACT

The binding affinity of ytterbium (Yb3+) and hafinum (Hf4+) to ligands of chemical entities of fragments of bermudagrass tissues and their resistance to exchanging Yb with other ligands and to displacement by protons were investigated. Chemical entities of acid resistant NDF (ARNDF), 0.1 N acid detergent fiber (0.1 N ADF), and permanganate cellulose (CELL) were prepared from fragments of bermudagrass hay (Cynodon dactylon [L.] Pers.) obtained by grinding to pass a 2-mm sieve. 175Ytterbium and Yb, as YbCl3, were initially bound to each preparation by soaking for 12 h in pH 5.5 borate buffer to obtain Yb bound onto ligands having affinity constants for Yb equal to or greater than that for the weakly stable borate ligand, Yb > or = borate. The fraction of Yb > or = borate was measured and fragments then sequentially exposed to acetate, citrate, nitrotriacetate (NTA), and EDTA ions to allow exchange of Yb from Yb > or = borate with ligands having affinity constants for Yb equal to or greater than acetate (Yb > or = acetate), citrate (Yb > or = citrate), NTA (Yb > or = NTA), and EDTA (Yb > or = EDTA) ions. Binding of Yb > or = borate indicated the existence of two species of ligands: strong ligands binding essentially 100% of added Yb at levels of 1 to 1,300 ppm (0.1 N ADF) and at 1 to 7,000 ppm (ARNDF); and weaker ligands binding 4 and 8% of the Yb, respectively, at levels of added Yb greater than 1,300 ppm and 7,000 ppm. Ytterbium > or = acetate of ARNDF, but not 0.1 N ADF, was as resistant to exchange as Yb > or = citrate. Ytterbium > or = borate was exchanged extensively (85% or greater) with soluble ligands having affinity constants > or = NTA. Ytterbium resistance to proton displacement at pH of 1.5 increased with Yb > or = EDTA > Yb > or = NTA > Yb > or = citrate > Yb > or = acetate. Very efficient binding of Yb to CELL suggested that such chemical preparations are not representative of native cellulose. Hafnium (4+) was strongly bound to plant tissues rendering both Hf and Hf-bound DM insoluble at a pH of 1.5 and insoluble in a modified NDF solvent without EDTA. It is concluded that Yb specifically applied as Yb > or = acetate and Hf4+ are indelible markers for estimating sojourn time of undigested plant tissues at the normal pH of the rumen. Because of its resistance to proton displacement, Hf4+ would be an indelible marker for estimating sojourn time in more acidic postgastric segments of the gastrointestinal tract.


Subject(s)
Cynodon/chemistry , Digestive System/metabolism , Hafnium/metabolism , Ytterbium/metabolism , Animals , Binding Sites , Binding, Competitive , Biomarkers/analysis , Dietary Fiber/metabolism , Digestion , Duodenum/metabolism , Hydrogen-Ion Concentration , Rumen/metabolism
7.
J Inorg Biochem ; 27(4): 255-70, 1986 Aug.
Article in English | MEDLINE | ID: mdl-3746294

ABSTRACT

The binding of hafnium to rat serum transferrin was studied using the time differential perturbed angular correlation (TDPAC) technique. Hafnium is interesting as a toxic metal binding to transferrin because it behaves metabolically similarly to plutonium. The isotope 181Hf offers favorable access to the TDPAC-method. Samples were prepared in vivo by intravenous injection of Hf-NTA, Hf-citrate, and Hf-oxalate solutions, respectively, into Sprague-Dawley rats and in vitro by adding Hf-NTA solution to fresh rat serum. In both cases two specific electric quadrupole interactions were observed, which correspond to two well-defined binding configurations. They may be attributed to the N-terminal and the C-terminal binding site in the transferrin molecule. The 181Hf-distribution between these two binding states depends on pH, salt and hafnium concentrations, temperature, and incubation time. With a fast TDPAC-setup of four BaF2-detectors a time resolution of about 600 ps could be achieved. The specific binding configurations of 181Hf and the comparatively slow relaxation times lead to spectra of considerable accuracy.


Subject(s)
Hafnium/metabolism , Transferrin/metabolism , Animals , Blood Proteins/metabolism , Hydrogen-Ion Concentration , Kinetics , Protein Binding , Radioisotopes , Rats , Rats, Inbred Strains
8.
Int J Rad Appl Instrum B ; 13(1): 21-9, 1986.
Article in English | MEDLINE | ID: mdl-3771235

ABSTRACT

Tumor uptake rates, concentrations in the mitochondrial fraction (containing lysosome) of liver and tumors, avid accumulations in connective tissue (especially inflammatory tissue) and binding substances in these tissues of 95Zr and 181Hf were essentially similar to those for 67Ga, 111In, 169Yb and 167Tm. However, the main binding substance of the above elements in group IV in tumor and liver was acid mucopolysaccharide whose molecular weight exceeded 40,000, although the above elements in group III were bound mainly to the acid mucopolysaccharide with a molecular weight of about 10,000.


Subject(s)
Hafnium , Liver/diagnostic imaging , Neoplasms, Experimental/diagnostic imaging , Zirconium , Animals , Carcinoma, Ehrlich Tumor/diagnostic imaging , Hafnium/metabolism , Kinetics , Liver/metabolism , Liver Neoplasms, Experimental/diagnostic imaging , Male , Mice , Neoplasms, Experimental/metabolism , Radioisotopes , Radionuclide Imaging , Rats , Rats, Inbred Strains , Sarcoma, Yoshida/diagnostic imaging , Subcellular Fractions/metabolism , Tissue Distribution , Zirconium/metabolism
9.
Br J Radiol ; 58(691): 655-9, 1985 Jul.
Article in English | MEDLINE | ID: mdl-4016497

ABSTRACT

The retention of 67Ga, 203Hg, 175 + 181Hf, 239Pu and 241Am in turpentine-induced abscesses and in normal muscle has been studied in rats for periods of up to 126 days after radionuclide injection (129 days after turpentine). The results show that although the uptake of 203Hg is about 7 times greater in the abscess than in control muscle, the half time of the nuclide is similar in both tissues, T1/2 = 5 days. The remaining radionuclides studied all show a similar retention time in control muscle, average T1/2 = 12.5 days, and a more prolonged retention in the abscess tissue, average T1/2 = 47 days, although in both control and abscess tissue the uptake of the radionuclides showed quite large metal-specific variations. It is concluded that for radionuclides which are transported on transferrin in the blood and which deposit in lysosomes within cells a common metal clearance mechanism may operate in normal muscle and a second general mechanism may operate in abscess tissue. The radionuclide concentration difference between normal and abscess tissue ranged from 8 (67Ga) to 27 (239Pu); thus the radiation dose delivered to the inflamed tissue was between about 30 and 100 times greater than in normal muscle.


Subject(s)
Abscess/metabolism , Muscular Diseases/metabolism , Radioisotopes/metabolism , Abscess/chemically induced , Americium/metabolism , Animals , Gallium Radioisotopes/metabolism , Hafnium/metabolism , Male , Mercury Radioisotopes/metabolism , Muscles/metabolism , Muscular Diseases/chemically induced , Plutonium/metabolism , Rats , Rats, Inbred Strains , Turpentine
10.
Int J Nucl Med Biol ; 12(5): 387-91, 1985.
Article in English | MEDLINE | ID: mdl-3833824

ABSTRACT

The whole body retention of 181Hf was studied in marmosets (Callithrex jacchus) and found to be closely similar to that in rats and Chinese hamsters. Limited tissue distribution studies suggest a higher uptake in liver and much lower deposition in skin and muscle in the marmoset as compared to the rat or Chinese hamster. Studies in Chinese hamsters showed that treatment with the chelating agent diethylenetriaminepentaacetic acid resulted in only a small reduction in the whole body retention of 181Hf. The absorption of orally administered 181Hf, in various chemical forms, was found to be between 0.04 and 0.13% of the ingested dose and was unaffected by age between 5 and 21 months but was increased by fasting. The measured absorption of 181Hf in Chinese hamsters and in rats was similar to that of plutonium suggesting that radiohafnium could be used as a surrogate for plutonium for selected studies in human volunteers.


Subject(s)
Hafnium/metabolism , Animals , Callithrix , Cricetinae , Cricetulus , Female , Intestinal Absorption , Kidney/metabolism , Liver/metabolism , Lung/metabolism , Male , Radioisotopes/metabolism , Tissue Distribution
11.
Radiat Res ; 95(2): 339-58, 1983 Aug.
Article in English | MEDLINE | ID: mdl-6611853

ABSTRACT

The metabolism of radiohafnium (175Hf + 181Hf) was studied in male Sprague-Dawley rats and Chinese hamsters for periods of up to 168 days. The results were compared with similar data for 239Pu in the same rat strain. In rats and hamsters the radiohafnium organ distribution was skeleton greater than skin greater than muscle greater than liver at about 7 days postinjection. Retention of radiohafnium and plutonium was similar in plasma and liver, as were the retention times observed for other organs: Absorption of radiohafnium from the gastrointestinal tract of rats was less than 0.05%. Biochemical studies showed that the radiohafnium was bound mainly to the iron-transport protein, transferrin, in blood plasma and in the liver cytosol of both the rat and the hamster, as has been observed also for plutonium. The metabolic behavior of radiohafnium mimics, to a large extent, that of plutonium, and it is suggested that radiohafnium can serve as a non-alpha-particle-emitting analog of plutonium for metabolic, biochemical, and selected human investigations.


Subject(s)
Hafnium/metabolism , Plutonium/metabolism , Animals , Cricetinae , Cricetulus , Hafnium/blood , Intestinal Absorption , Male , Plutonium/blood , Radioisotopes/metabolism , Rats , Rats, Inbred Strains , Tissue Distribution
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