Single-Stage Microfluidic Synthesis Route for BaGdF5:Tb3+-Based Nanocomposite Materials: Synthesis, Characterization and Biodistribution.

Rare-earth-doped nanoscaled BaGdF5 is known as an efficient contrasting agent for X-ray micro-CT and NMR as well as a promising candidate for X-ray photodynamic therapy, thereby opening an opportunity for theragnostic applications. Conventional synthesis of Ln-doped BaGdF5 consider a long-lasting batch procedure, while a conjugation with photosensitizer usually implies a separate stage requiring active mixing. To the best of our knowledge, in this work, we for the first time obtain BaGdF5:Tb3+ nanophosphors in a microfluidic route at temperatures as low as 100 °C while decreasing the time of thermal treatment down to 6 min. The proposed synthesis route allows for the obtaining of single-phase and monodisperse BaGd1-xF5:Tbx3+ nanoparticles with an averaged particle size of ca. 7-9 nm and hydrodynamic radius around 22 nm, as estimated from TEM and DLS, respectively. In addition, X-ray-excited optical luminescence has been recorded in situ for the series of nanophosphors synthesis with varied flow rates of Tb3+ and Gd3+ stock solutions, thereby anticipating a possible application of microfluidics for screening a wide range of possible co-dopants and reaction conditions and its effect on the optical properties of the synthesized materials. Moreover, we demonstrated that BaGd1-xF5:Tbx3+@RoseBengal conjugates might be obtained in a single-stage route by implementing an additional mixer at the synthesis outcome, namely, by mixing the resulting reaction mixture containing nanoparticles with an equivalent flow of photosensitizer aqueous solution. In vitro cytotoxicity test declares moderate toxicity effect on different cell lines, while the results of flow cytometry indirectly confirm cellular uptake. Finally, we report long-term biodistribution monitoring of the synthesized nanocomposites assessed by X-ray micro-CT in the in vivo experiments on balb/c mice, which depicts an unusual character of agents' accumulation.

Doxorubicin-Loaded Core-Shell UiO-66@SiO2 Metal-Organic Frameworks for Targeted Cellular Uptake and Cancer Treatment.

Beneficial features of biocompatible high-capacity UiO-66 nanoparticles, mesoporous SiO2, and folate-conjugated pluronic F127 were combined to prepare the core-shell UiO-66@SiO2/F127-FA drug delivery carrier for targeted cellular uptake in cancer treatment. UiO-66 and UiO-66-NH2 nanoparticles with a narrow size and shape distribution were used to form a series of core-shell MOF@SiO2 structures. The duration of silanization was varied to change the thickness of the SiO2 shell, revealing a nonlinear dependence that was attributed to silicon penetration into the porous MOF structure. Doxorubicin encapsulation showed a similar final loading of 5.6 wt % for both uncoated and silica-coated particles, demonstrating the potential of the nanocomposite's application in small molecule delivery. Silica coating improved the colloidal stability of the composites in a number of model physiological media, enabled grafting of target molecules to the surface, and prevented an uncontrolled release of their cargo, with the drawback of decreased overall porosity. Further modification of the particles with the conjugate of pluronic and folic acid was performed to improve the biocompatibility, prolong the blood circulation time, and target the encapsulated drug to the folate-expressing cancer cells. The final DOX-loaded UiO-66@SiO2/F127-FA nanoparticles were subjected to properties characterization and in vitro evaluation, including studies of internalization into cells and antitumor activity. Two cell lines were used: MCF-7 breast cancer cells, which have overexpressed folate receptors on the cell membranes, and RAW 264.7 macrophages without folate overexpression. These findings will provide a potential delivery system for DOX and increase the practical value of MOFs.

Candidate Tidal Disruption Event AT2019fdr Coincident with a High-Energy Neutrino.

The origins of the high-energy cosmic neutrino flux remain largely unknown. Recently, one high-energy neutrino was associated with a tidal disruption event (TDE). Here we present AT2019fdr, an exceptionally luminous TDE candidate, coincident with another high-energy neutrino. Our observations, including a bright dust echo and soft late-time x-ray emission, further support a TDE origin of this flare. The probability of finding two such bright events by chance is just 0.034%. We evaluate several models for neutrino production and show that AT2019fdr is capable of producing the observed high-energy neutrino, reinforcing the case for TDEs as neutrino sources.

Operando Photo-Electrochemical Catalysts Synchrotron Studies.

The attempts to develop efficient methods of solar energy conversion into chemical fuel are ongoing amid climate changes associated with global warming. Photo-electrocatalytic (PEC) water splitting and CO2 reduction reactions show high potential to tackle this challenge. However, the development of economically feasible solutions of PEC solar energy conversion requires novel efficient and stable earth-abundant nanostructured materials. The latter are hardly available without detailed understanding of the local atomic and electronic structure dynamics and mechanisms of the processes occurring during chemical reactions on the catalyst-electrolyte interface. This review considers recent efforts to study photo-electrocatalytic reactions using in situ and operando synchrotron spectroscopies. Particular attention is paid to the operando reaction mechanisms, which were established using X-ray Absorption (XAS) and X-ray Photoelectron (XPS) Spectroscopies. Operando cells that are needed to perform such experiments on synchrotron are covered. Classical and modern theoretical approaches to extract structural information from X-ray Absorption Near-Edge Structure (XANES) spectra are discussed.

Synthesis, Characterization and Biodistribution of GdF3:Tb3+@RB Nanocomposites.

Herein we report the development of a nanocomposite for X-ray-induced photodynamic therapy (X-PDT) and computed tomography (CT) based on PEG-capped GdF3:Tb3+ scintillating nanoparticles conjugated with Rose Bengal photosensitizer via electrostatic interactions. Scintillating GdF3:Tb3+ nanoparticles were synthesized by a facile and cost-effective wet chemical precipitation method. All synthesized nanoparticles had an elongated "spindle-like" clustered morphology with an orthorhombic structure. The structure, particle size, and morphology were determined by transmission electron microscopy (TEM), X-ray diffraction (XRD), and dynamic light scattering (DLS) analysis. The presence of a polyethylene glycol (PEG) coating and Rose Bengal conjugates was proved by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG), and ultraviolet-visible (UV-vis) analysis. Upon X-ray irradiation of the colloidal PEG-capped GdF3:Tb3+-Rose Bengal nanocomposite solution, an efficient fluorescent resonant energy transfer between scintillating nanoparticles and Rose Bengal was detected. The biodistribution of the synthesized nanoparticles in mice after intravenous administration was studied by in vivo CT imaging.

Loading of the Model Amino Acid Leucine in UiO-66 and UiO-66-NH2: Optimization of Metal-Organic Framework Carriers and Evaluation of Host-Guest Interactions.

Two metal-organic frameworks (MOFs), UiO-66 and UiO-66-NH2, were considered as containers for bioactive chemicals. We provide a synthesis technique, which allowed the production of these materials suitable for biomedical applications. Both MOFs were characterized as single-phase porous materials composed of nanoparticles (30-65 nm) with a ζ-potential of more than 40 mV in water suspension. D,L-Leucine was applied as a model molecule, which allowed us to trace the mechanism of the loading process. We showed that after synthesis, amino groups of UiO-66-NH2 are coordinated with solvent residuals. It results in a similar route of leucine loading in UiO-66 and UiO-66-NH2 samples. Using joint data of thermogravimetric analysis and calorimetry, infrared spectroscopy, and nitrogen adsorption, we revealed that methyl groups of leucine molecules are responsible for bonding of an MOF matrix. We proposed the formation of bonds between CH3 groups and benzene rings of linkers via CH-π interaction. We also assessed the toxicity of the synthesized MOFs toward HeLa cells at 50 µg/mL after 24 h incubation and revealed no negative effects on the viability of the cells, prompting further biomedical research in the areas of small-molecule delivery and cell signaling and metabolism modulation.

Self-Driving Laboratories for Development of New Functional Materials and Optimizing Known Reactions.

Innovations often play an essential role in the acceleration of the new functional materials discovery. The success and applicability of the synthesis results with new chemical compounds and materials largely depend on the previous experience of the researcher himself and the modernity of the equipment used in the laboratory. Artificial intelligence (AI) technologies are the next step in developing the solution for practical problems in science, including the development of new materials. Those technologies go broadly beyond the borders of a computer science branch and give new insights and practical possibilities within the far areas of expertise and chemistry applications. One of the attractive challenges is an automated new functional material synthesis driven by AI. However, while having many years of hands-on experience, chemistry specialists have a vague picture of AI. To strengthen and underline AI's role in materials discovery, a short introduction is given to the essential technologies, and the machine learning process is explained. After this review, this review summarizes the recent studies of new strategies that help automate and accelerate the development of new functional materials. Moreover, automatized laboratories' self-driving cycle could benefit from using AI algorithms to optimize new functional nanomaterials' synthetic routes. Despite the fact that such technologies will shape material science in the nearest future, we note the intelligent use of algorithms and automation is required for novel discoveries.

ᶫ-Leucine Loading and Release in MIL-100 Nanoparticles.

Synthesis of the MIL-100 metal-organic framework particles was carried out by hydrothermal (HT) and microwave (MW)-assisted methods. Transmission electron microscopy showed formation of microparticles in the course of hydrothermal synthesis and nanoparticles for microwave-assisted synthesis. Powder X-ray diffraction confirmed formation of larger crystallites for hydrothermal synthesis. Particle aggregation in aqueous solution was observed by dynamic light scattering. However, the stability of both samples could be improved in acetic acid solution. Nitrogen sorption isotherms showed high porosity of the particles. ᶫ-leucine molecule was used as a model molecule for loading in the porous micro- and nanoparticles. Loading was estimated by FTIR spectroscopy and thermogravimetric analysis. UV-VIS spectroscopy quantified ᶫ-leucine release from the particles in aqueous solution. Cytotoxicity studies using the HeLa cell model showed that the original particles were somewhat toxic, but ᶫ-leucine loading ameliorated the toxic effects, likely due to signaling properties of the amino acid.

Vaporization and thermodynamics of ceramics in the Sm2 O3 -Y2 O3 -HfO2 system.

RATIONALE: The Sm2 O3 -Y2 O3 -HfO2 system holds promise for applications in the sphere of high-temperature technologies, particularly the development of ultra-high-temperature ceramics. However, the reliability of refractory materials is dependent on the possible selective vaporization of their components leading to changes in their physicochemical properties. Thus, information about vaporization processes and thermodynamic properties of ceramics based on the Sm2 O3 -Y2 O3 -HfO2 system may be of importance for the production of high-temperature materials as well as for the prediction of the physicochemical properties of ultra-high-temperature ceramics. METHODS: The Knudsen effusion mass spectrometric method was used, with an MS-1301 magnetic mass spectrometer equipped with a tungsten twin effusion cell used to examine the samples in the Sm2 O3 -Y2 O3 -HfO2 system. Electron ionization of vapor species effusing from the cell was carried out at an ionization energy of 25 eV. RESULTS: It was shown that at a temperature of 2373 K, selective vaporization of Sm2 O3 and Y2 O3 occurred in the samples of the Sm2 O3 -Y2 O3 -HfO2 system, with the main vapor species being SmO, Sm, YO, and O. The partial pressures of these vapor species were obtained by the ion current comparison method. The Sm2 O3 activities in the Sm2 O3 -Y2 O3 -HfO2 system were determined and allowed the evaluation of the excess Gibbs energies at 2373 K. The direction of change of the condensed phase of the samples because of selective vaporization of the components was examined. CONCLUSIONS: The Sm2 O3 -Y2 O3 -HfO2 system was characterized by negative deviations from the ideal behavior at 2373 K. The excess Gibbs energies evaluated in the present study were approximated using the Redlich-Kister representation and visualized in the form of curves of constant values in the concentration triangle. The data obtained in the Sm2 O3 -Y2 O3 -HfO2 system were optimized using the Barker-Guggenheim theory of associated solutions.

Global Variation in Use of Enteral Nutrition for Pediatric Crohn Disease.

OBJECTIVES: Exclusive enteral nutrition (EEN) is an effective induction treatment for pediatric Crohn disease. Given the center-based variation in use and diversity in practice, we constructed a survey aimed at sharing experience and strategies in administering EEN, stimulating further research, and optimizing therapy. METHODS: This survey was constructed after consultation with experts and designed to address key knowledge gaps. The survey was disseminated through the Pediatric IBD Porto Group of ESPGHAN, Canadian Children IBD Network, selective experts, and was sent twice through the Pediatric Gastrointestinal-Bulletin Board (PEDGI-BB). Data were collected into REDCap and analyzed using descriptive statistics. RESULTS: In total, 146 participants from 26 countries completed the survey. Sixty-five percentage of participants were general, non-inflammatory bowel diseases (IBD)-focused pediatric gastroenterologists, 21% were IBD-focused, and 10% were dietitians. The most common indications (∼90% use) were for ileocecal and ileocolonic disease (Paris L1 and L3). The most common duration was 8 weeks and 66% preferred oral to nasogastric administration. Most (63%) did not allow any additional intake and 69% instructed patients to continue partial enteral nutrition (EN) after completing treatment. Dietitians were identified as essential to EEN success while the primary challenges of EEN programs were adherence and lack of support. Regional and professional practice differences were observed in EEN indication, age, exclusivity, program structure/support, and cost coverage. CONCLUSIONS: We found significant variation in practice and use of EEN with several regional and professional differences. Global variation offers opportunities for research and improving care. This survey establishes a framework and provides resources for collaboration and information sharing.

Doxorubicin pharmacokinetics in lymphoma patients treated with doxorubicin-loaded eythrocytes.

Doxorubicin-loaded erythrocytes (DLE) were administrated to 15 lymphoma patients. Antibiotic peak concentration in blood decreased by 55%, doxorubicin circulated several times longer, and the area under the concentration-time curve increased 5 times if compared with standard doxorubicin administration. The DLE was well tolerated by patients.