Large-Scale Engineerable Films Tailored with Cellulose Nanofibrils for Lighting Management and Thermal Insulation.

Fibrillated cellulose-based nanocomposites can improve energy efficiency of building envelopes, especially windows, but efficiently engineering them with a flexible ability of lighting and thermal management remains highly challenging. Herein, a scalable interfacial engineering strategy is developed to fabricate haze-tunable thermal barrier films tailored with phosphorylated cellulose nanofibrils (PCNFs). Clear films with an extremely low haze of 1.6% (glass-scale) are obtained by heat-assisted surface void packing without hydrophobization of nanocellulose. PCNF gel cakes serve here as templates for surface roughening, thereby resulting in a high haze (73.8%), and the roughened films can block heat transfer by increasing solar reflection in addition to a reduced thermal conduction. Additionally, obtained films can tune distribution of light from visible to near-infrared spectral range, enabling uniform colored lighting and inhibiting localized heating. Furthermore, an integrated simulation of lighting and cooling energy consumption in the case of office buildings shows that the film can reduce the total energy use by 19.2-38.1% under reduced lighting levels. Such a scalable and versatile engineering strategy provides an opportunity to endow nanocellulose-reinforced materials with tunable optical and thermal functionalities, moving their practical applications in green buildings forward.

Capturing Mercury-197m/g for Auger Electron Therapy and Cancer Theranostic with Sulfur-Containing Cyclen-Based Macrocycles.

The interest in mercury radioisotopes, 197mHg (t1/2 = 23.8 h) and 197gHg (t1/2 = 64.14 h), has recently been reignited by the dual diagnostic and therapeutic nature of their nuclear decays. These isotopes emit γ-rays suitable for single photon emission computed tomography imaging and Auger electrons which can be exploited for treating small and metastatic tumors. However, the clinical utilization of 197m/gHg radionuclides is obstructed by the lack of chelators capable of securely binding them to tumor-seeking vectors. This work aims to address this challenge by investigating a series of chemically tailored macrocyclic platforms with sulfur-containing side arms, namely, 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO3S), and 1,7-bis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,10-diacetic acid (DO2A2S). 1,4,7,10-Tetrazacyclododecane-1,4,7,10-tetracetic acid (DOTA), the widest explored chelator in nuclear medicine, and the nonfunctionalized backbone 1,4,7,10-tetrazacyclododecane (cyclen) were considered as well to shed light on the role of the sulfanyl arms in the metal coordination. To this purpose, a comprehensive experimental and theoretical study encompassing aqueous coordination chemistry investigations through potentiometry, nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography, and density functional theory (DFT) calculations, as well as concentration- and temperature-dependent [197m/gHg]Hg2+ radiolabeling and in vitro stability assays in human serum was conducted. The obtained results reveal that the investigated chelators rapidly complex Hg2+ in aqueous media, forming extremely thermodynamically stable 1:1 metal-to-ligand complexes with superior stabilities compared to those of DOTA or cyclen. These complexes exhibited 6- to 8-fold coordination environments, with donors statically bound to the metal center, as evidenced by the presence of 1H-199Hg spin-spin coupling via NMR. A similar octacoordinated environment was also found for DOTA in both solution and solid state, but in this case, multiple slowly exchanging conformers were detected at ambient temperature. The sulfur-rich ligands quantitatively incorporate cyclotron-produced [197m/gHg]Hg2+ under relatively mild reaction conditions (pH = 7 and T = 50 °C), with the resulting radioactive complexes exhibiting decent stability in human serum (up to 75% after 24 h). By developing viable chelators and understanding the impact of structural modifications, our research addresses the scarcity of suitable chelating agents for 197m/gHg, offering promise for its future in vivo application as a theranostic Auger-emitter radiometal.

Selective Chelation of the Exotic Meitner-Auger Emitter Mercury-197 m/g with Sulfur-Rich Macrocyclic Ligands: Towards the Future of Theranostic Radiopharmaceuticals.

Mercury-197 m/g are a promising pair of radioactive isomers for incorporation into a theranostic as they can be used as a diagnostic agent using SPECT imaging and a therapeutic via Meitner-Auger electron emissions. However, the current absence of ligands able to stably coordinate 197m/g Hg to a tumour-targeting vector precludes their use in vivo. To address this, we report herein a series of sulfur-rich chelators capable of incorporating 197m/g Hg into a radiopharmaceutical. 1,4,7,10-Tetrathia-13-azacyclopentadecane (NS4 ) and its derivatives, (2-(1,4,7,10-tetrathia-13-azacyclopentadecan-13-yl)acetic acid (NS4 -CA) and N-benzyl-2-(1,4,7,10-tetrathia-13-azacyclopentadecan-13-yl)acetamide (NS4 -BA), were designed, synthesized and analyzed for their ability to coordinate Hg2+ through a combination of theoretical (DFT) and experimental coordination chemistry studies (NMR and mass spectrometry) as well as 197m/g Hg radiolabeling studies and in vitro stability assays. The development of stable ligands for 197m/g Hg reported herein is extremely impactful as it would enable their use for in vivo imaging and therapy, leading to personalized treatments for cancer.

Exploration of commercial cyclen-based chelators for mercury-197 m/g incorporation into theranostic radiopharmaceuticals.

A comprehensive investigation of the Hg2+ coordination chemistry and 197m/gHg radiolabeling capabilities of cyclen-based commercial chelators, namely, DOTA and DOTAM (aka TCMC), along with their bifunctional counterparts, p-SCN-Bn-DOTA and p-SCN-Bn-TCMC, was conducted to assess the suitability of these frameworks as bifunctional chelators for the 197m/gHg2+ theranostic pair. Radiolabeling studies revealed that TCMC and DOTA exhibited low radiochemical yields (0%-6%), even when subjected to harsh conditions (80°C) and high ligand concentrations (10-4 M). In contrast, p-SCN-Bn-TCMC and p-SCN-Bn-DOTA demonstrated significantly higher 197m/gHg radiochemical yields (100% ± 0.0% and 70.9% ± 1.1%, respectively) under the same conditions. The [197 m/gHg]Hg-p-SCN-Bn-TCMC complex was kinetically inert when challenged against human serum and glutathione. To understand the differences in labeling between the commercial chelators and their bifunctional counterparts, non-radioactive natHg2+ complexes were assessed using NMR spectroscopy and DFT calculations. The NMR spectra of Hg-TCMC and Hg-p-SCN-Bn-TCMC suggested binding of the Hg2+ ion through the cyclen backbone framework. DFT studies indicated that binding of the Hg2+ ion within the backbone forms a thermodynamically stable product. However, competition can form between isothiocyanate binding and binding through the macrocycle, which was experimentally observed. The isothiocyanate bound coordination product was dominant at the radiochemical scale as, in comparison, the macrocycle bound product was seen at the NMR scale, agreeing with the DFT result. Furthermore, a bioconjugate of TCMC (TCMC-PSMA) targeting prostate-specific membrane antigen was synthesized and radiolabeled, resulting in an apparent molar activity of 0.089 MBq/nmol. However, the complex demonstrated significant degradation over 24 h when exposed to human serum and glutathione. Subsequently, cell binding assays were conducted, revealing a Ki value ranging from 19.0 to 19.6 nM. This research provides crucial insight into the effectiveness of current commercial chelators in the context of 197m/gHg2+ radiolabeling. It underscores the necessity for the development of specific and customized chelators to these unique "soft" radiometals to advance 197m/gHg2+ radiopharmaceuticals.

Efficient removal of chloroform from groundwater using activated percarbonate by cellulose nanofiber-supported Fe/Cu nanocomposites.

Chloroform (CF) is a recalcitrant halogenated methane (HM) that has received widespread attention due to its frequent detection in groundwater and its potential carcinogenic risk. In this study, TEMPO-oxidized cellulose nanofiber-supported iron/copper bimetallic nanoparticles (TOCNF-Fe/Cu), a novel composite catalyst, was synthesized to activate sodium percarbonate (SPC) for the removal of CF from groundwater. The results showed that over 96.3% of CF could be removed in a neutral reaction medium (pH 6.5-9) within 180 min using 0.66 g L-1 of TOCNF (0.32)-Fe/Cu (1) and 1 mM of SPC, which outperforms typical advanced oxidation processes. The reaction mechanism of the TOCNF-Fe/Cu-SPC system for the CF removal was elucidated. As demonstrated through electron paramagnetic resonance and quenching experiments, the TOCNF-Fe/Cu-SPC system was found to include •OH and O2•-, where the latter played a dominant role in the CF removal. DFT calculations indicated that TOCNF improved the electron transport capability of Fe/Cu and reduced the transition state energy. The Fe species on the surface of TOCNF-Fe/Cu were identified as the primary active sites for SPC activation, whereas the Cu species were beneficial to the regeneration of the Fe species. Additionally, TOCNF-Fe/Cu was found to have good recyclability and stability. The feasibility of the TOCNF-Fe/Cu-SPC system was further confirmed by applying it for the efficient removal of composite HMs from actually contaminated groundwater. Overall, the TOCNF-Fe/Cu-SPC system is an attractive candidate for the treatment of HM-contaminated groundwater.

Determination of distribution coefficients of mercury and gold on selected extraction chromatographic resins - towards an improved separation method of mercury-197 from proton-irradiated gold targets.

Radioisotope mercury-197g (197gHg, half-life: 64.14 h) along with its metastable isomer (197mHg, half-life: 23.8 h) are potential candidates for targeted Meitner-Auger electron therapy due to their suitable decay properties. Their production can be achieved via proton irradiation of a natural gold target, but the number of studies surrounding their separation from an irradiated gold target is limited. This study focuses on the determination of distribution coefficients (Kd) of gold (III) and mercury (II) on seven extraction chromatographic resins. Mercury Kd were measured by means of radiotracers and Inductively Coupled Plasma Mass Spectrometry (ICP_MS); values obtained from the two methods were generally in good agreement. These results can provide insight on Hg and Au chemistry and aid in the design of improved separation system(s).

Production and radiochemistry of antimony-120m: Efforts toward Auger electron therapy with 119Sb.

Targeted Meitner-Auger Therapy (TMAT) has potential for personalized treatment thanks to its subcellular dosimetric selectivity, which is distinct from the dosimetry of ß- and α particle emission based Targeted Radionuclide Therapy (TRT). To date, most clinical and preclinical TMAT studies have used commercially available radionuclides. These studies showed promising results despite using radionuclides with theoretically suboptimal photon to electron ratios, decay kinetics, and electron emission spectra. Studies using radionuclides whose decay characteristics are considered more optimal are therefore important for evaluation of the full potential of Meitner-Auger therapy; 119Sb is among the best such candidates. In the present work, we develop radiochemical purification of 120Sb from irradiated natural tin targets for TMAT studies with 119Sb.

Integrating direct reuse and extraction recovery of TEMPO for production of cellulose nanofibrils.

TEMPO-oxidized cellulose nanofibrils (CNFs) possess lots of attractive properties. However, recycling of TEMPO is desirable because of ecological and economic demands. In this study, a novel strategy integrating direct reuse and extraction recovery of TEMPO was developed. 50 % of filtrates after TEMPO oxidation were directly reused and half of the fresh TEMPO was added to maintain a constant dosage, the obtained CNFs within 2 cycles shared similar carboxylate contents, crystallinity, and homogeneous width compared to the original ones. Furthermore, TEMPO in another 50 % of filtrates was extracted by ethyl acetate followed by distillation. The CNFs produced using the extracted TEMPO had almost the same properties compared to those of original ones, suggesting a negligible loss of activity of the recovered catalyst. Compared to the traditional route, the combined strategy exhibited a 31.3 % reduction in production costs, which enables clean and cost-effective production of CNFs and shows a promising industrial feasibility.

Ultrastrong and flame-retardant microfibers via microfluidic wet spinning of phosphorylated cellulose nanofibrils.

Translation of the high mechanical properties of cellulose nanofibrils (CNFs) to macroscopic fibers represents a great challenge due to difficulties in the assembly of CNFs into well-ordered structures. In this study, we report the ultrastrong and flame-retardant microfibers via the microfluidic wet spinning of phosphorylated cellulose nanofibrils (PCNFs) with high charge content. The macroscopic stress is effectively transferred to the individual PCNFs and results in a Young's modulus of 29 GPa and a tensile strength of 654 MPa. The as-prepared microfibers retain >85 % strength in the wet hydration state, exceeding most natural or synthetic microfibers. Furthermore, glycerol and egg yolk were introduced to the microfibers for enhancing the modulus (31 GPa), strength (865 MPa) and the strain to failure (10.95 %). In addition, the PCNFs microfibers have good flame retardancy. This study expands the potential applications of nanocellulose microfibers in biomedical and flame-retardant materials.

Oligomeric procyanidins inhibit insulin fibrillation by forming unstructured and off-pathway aggregates.

ß-sheet-rich amyloid fibril or aggregate accumulation has been implicated in a number of human diseases. Numerous studies demonstrate that natural polyphenols decrease the risk of degenerative diseases and inhibit in vitro amyloid formation. However, the molecular mechanism for the anti-amyloidogenesis of polyphenols is still unclear. Thus, this study investigates the effects of oligomeric procyanidins (OPCs), resveratrol, and trehalose on the amyloidogenicity of insulin via thioflavin-T (ThT) fluorescence, dynamic light scattering (DLS), circular dichroism (CD), and transmission electronic microscopy (TEM). The results demonstrate that the order of inhibitory effects on insulin amyloid fibrillation is OPCs > resveratrol > trehalose, suggesting that the polyphenolic structure is important for fibril deposition. OPCs show potent inhibitory effects at all stages of insulin fibrillation and redirect the insulin aggregation pathway via the formation of unstructured, off-pathway aggregates. These findings contribute to the development of novel anti-amyloidogenic products from naturally occurring materials.

Meitner-Auger Electron Emitters for Targeted Radionuclide Therapy: Mercury-197m/g and Antimony-119

Targeted Radionuclide Therapies (TRTs) based on Auger emitting radionuclides have the potential to deliver extremely selective therapeutic payloads on the cellular level. However, to fully exploit this potential, suitable radionuclides need to be applied in combination with appropriate delivery systems. In this review, we summarize the state-of-the-art production, purification, chelation and applications of two promising candidates for Targeted Auger Therapy, namely antimony- 119 (119Sb) and mercury-197 (197Hg). Both radionuclides have great potential to become efficient tools for TRT. We also highlight our current progress on the production of both radionuclides at TRIUMF and the University of Wisconsin.

Interaction of particles with mucosae and cell membranes.

The fates and detrimental effects of particles entering the body have gained increasingly notable attention worldwide because of the burgeoning applications of various particles and wide existence of ambient particulate matter. Studies on the interaction of particles with biological interfaces demonstrate the potential risks and hazards to the health of living organisms. This review aims to provide a systematic overview of the interaction between particles and typical biological interfaces, with an emphasis on the effects of particle properties and microenvironment, and the potential adverse results arising from these interactions. First, we describe the major entry routes of particles into the human body to understand the main exposure pathways and the fates and impacts of particles. Different behaviors of particles interacting with mucosae and cell membranes are then reviewed. Finally, the knowledge gaps are identified and the long-term development of interaction research is proposed.

Nontoxic Black Phosphorus Quantum Dots Inhibit Insulin Amyloid Fibrillation at an Ultralow Concentration.

Amyloid are protein aggregates formed by cross ß structures assemblies. Inhibiting amyloid aggregation or facilitating its disassembly are considered to be two major effective therapeutic strategies in diseases involving peptide or protein fibrillation such Alzheimer's disease or diabetes. Using thioflavin-T fluorescence, far-UV circular dichroism spectroscopy, and atomic force microscopy, we found nontoxic and biocompatible black phosphorus quantum dots (BPQDs) appear to have an exceptional capacity to inhibit insulin aggregation and to disassemble formed mature fibrils, even at an ultralow concentration (100 ng/mL). The inhibition of fibrillation persists at all stages of insulin aggregation and increases PC12 cells survival when exposed to amyloid fibrils. Molecular dynamics simulations suggest that BPQDs are able to stabilize the α-helix structure of insulin and obliterate the ß-sheet structure to promote the fibril formation. These characteristics make BPQDs be promising candidate in preventing amyloidosis, disease treatment, as well as in the storage and processing of insulin.