Covalent targeted radioligands potentiate radionuclide therapy.

Targeted radionuclide therapy, in which radiopharmaceuticals deliver potent radionuclides to tumours for localized irradiation, has addressed unmet clinical needs and improved outcomes for patients with cancer1-4. A therapeutic radiopharmaceutical must achieve both sustainable tumour targeting and fast clearance from healthy tissue, which remains a major challenge5,6. A targeted ligation strategy that selectively fixes the radiopharmaceutical to the target protein in the tumour would be an ideal solution. Here we installed a sulfur (VI) fluoride exchange (SuFEx) chemistry-based linker on radiopharmaceuticals to prevent excessively fast tumour clearance. When the engineered radiopharmaceutical binds to the tumour-specific protein, the system undergoes a binding-to-ligation transition and readily conjugates to the tyrosine residues through the 'click' SuFEx reaction. The application of this strategy to a fibroblast activation protein (FAP) inhibitor (FAPI) triggered more than 80% covalent binding to the protein and almost no dissociation for six days. In mice, SuFEx-engineered FAPI showed 257% greater tumour uptake than did the original FAPI, and increased tumour retention by 13-fold. The uptake in healthy tissues was rapidly cleared. In a pilot imaging study, this strategy identified more tumour lesions in patients with cancer than did other methods. SuFEx-engineered FAPI also successfully achieved targeted ß- and α-radionuclide therapy, causing nearly complete tumour regression in mice. Another SuFEx-engineered radioligand that targets prostate-specific membrane antigen (PSMA) also showed enhanced therapeutic efficacy. Considering the broad scope of proteins that can potentially be ligated to SuFEx warheads, it might be possible to adapt this strategy to other cancer targets.

Chemical gradients in human enamel crystallites.

Dental enamel is a principal component of teeth1, and has evolved to bear large chewing forces, resist mechanical fatigue and withstand wear over decades2. Functional impairment and loss of dental enamel, caused by developmental defects or tooth decay (caries), affect health and quality of life, with associated costs to society3. Although the past decade has seen progress in our understanding of enamel formation (amelogenesis) and the functional properties of mature enamel, attempts to repair lesions in this material or to synthesize it in vitro have had limited success4-6. This is partly due to the highly hierarchical structure of enamel and additional complexities arising from chemical gradients7-9. Here we show, using atomic-scale quantitative imaging and correlative spectroscopies, that the nanoscale crystallites of hydroxylapatite (Ca5(PO4)3(OH)), which are the fundamental building blocks of enamel, comprise two nanometric layers enriched in magnesium flanking a core rich in sodium, fluoride and carbonate ions; this sandwich core is surrounded by a shell with lower concentration of substitutional defects. A mechanical model based on density functional theory calculations and X-ray diffraction data predicts that residual stresses arise because of the chemical gradients, in agreement with preferential dissolution of the crystallite core in acidic media. Furthermore, stresses may affect the mechanical resilience of enamel. The two additional layers of hierarchy suggest a possible new model for biological control over crystal growth during amelogenesis, and hint at implications for the preservation of biomarkers during tooth development.

The effect of pseudoknot base pairing on cotranscriptional structural switching of the fluoride riboswitch.

A central question in biology is how RNA sequence changes influence dynamic conformational changes during cotranscriptional folding. Here we investigated this question through the study of transcriptional fluoride riboswitches, non-coding RNAs that sense the fluoride anion through the coordinated folding and rearrangement of a pseudoknotted aptamer domain and a downstream intrinsic terminator expression platform. Using a combination of Escherichia coli RNA polymerase in vitro transcription and cellular gene expression assays, we characterized the function of mesophilic and thermophilic fluoride riboswitch variants. We showed that only variants containing the mesophilic pseudoknot function at 37°C. We next systematically varied the pseudoknot sequence and found that a single wobble base pair is critical for function. Characterizing thermophilic variants at 65°C through Thermus aquaticus RNA polymerase in vitro transcription showed the importance of this wobble pair for function even at elevated temperatures. Finally, we performed all-atom molecular dynamics simulations which supported the experimental findings, visualized the RNA structure switching process, and provided insight into the important role of magnesium ions. Together these studies provide deeper insights into the role of riboswitch sequence in influencing folding and function that will be important for understanding of RNA-based gene regulation and for synthetic biology applications.

Naphthalimide-based new architecture for fluorescence turn-on sensing of Cu2+ and colorimetric detection of F-/CN.

A new molecular structure 1 has been developed on naphthalimide motif. The amine and triazole binding groups have been employed at the 4-position of naphthalimide to explore the sensing behavior of molecule 1. Single crystal x-ray diffraction and other spectroscopic techniques confirm the identity of 1. Compound 1 exhibits high selectivity and sensitivity for Cu2+ ions in CH3CN. The binding of Cu2+ shows âˆ¼ 70-fold enhancement in emission at 520 nm. The binding follows 1:1 interaction and the detection limit is determined to be 6.49 × 10-7 M. The amine-triazole binding site in 1 also corroborates the detection of F- through a colour change in CH3CN. Initially H-bonding and then deprotonation of amine -NH- in the presence of F- are the sequential steps involved in F- recognition with a detection limit of 4.13 × 10-7 M. Compound 1 is also sensible to CN- like F- ion and they are distinguished by Fe3+ ion. Cu2+-ensemble of 1 fluorimetrically recognizes F- among the tested anions and vice-versa. The collaborative effect of amine and triazole motifs in the binding of both Cu2+ and F-/CN- has been explained by DFT calculation.

Straightforward access to N-trifluoromethyl amides, carbamates, thiocarbamates and ureas.

Amides and related carbonyl derivatives are of central importance across the physical and life sciences1,2. As a key biological building block, the stability and conformation of amides affect the structures of peptides and proteins as well as their biological function. In addition, amide-bond formation is one of the most frequently used chemical transformations3,4. Given their ubiquity, a technology that is capable of modifying the fundamental properties of amides without compromising on stability may have considerable potential in pharmaceutical, agrochemical and materials science. In order to influence the physical properties of organic molecules-such as solubility, lipophilicity, conformation, pKa and (metabolic) stability-fluorination approaches have been widely adopted5-7. Similarly, site-specific modification with isosteres and peptidomimetics8, or in particular by N-methylation9, has been used to improve the stability, physical properties, bioactivities and cellular permeabilities of compounds. However, the N-trifluoromethyl carbonyl motif-which combines both N-methylation and fluorination approaches-has not yet been explored, owing to a lack of efficient methodology to synthesize it. Here we report a straightforward method to access N-trifluoromethyl analogues of amides and related carbonyl compounds. The strategy relies on the operationally simple preparation of bench-stable carbamoyl fluoride building blocks, which can be readily diversified to the corresponding N-CF3 amides, carbamates, thiocarbamates and ureas. This method tolerates rich functionality and stereochemistry, and we present numerous examples of highly functionalized compounds-including analogues of widely used drugs, antibiotics, hormones and polymer units.

Diversity oriented clicking delivers ß-substituted alkenyl sulfonyl fluorides as covalent human neutrophil elastase inhibitors.

Diversity Oriented Clicking (DOC) is a discovery method geared toward the rapid synthesis of functional libraries. It combines the best attributes of both classical and modern click chemistries. DOC strategies center upon the chemical diversification of core "SuFExable" hubs-exemplified by 2-Substituted-Alkynyl-1-Sulfonyl Fluorides (SASFs)-enabling the modular assembly of compounds through multiple reaction pathways. We report here a range of stereoselective Michael-type addition pathways from SASF hubs including reactions with secondary amines, carboxylates, 1H-1,2,3-triazole, and halides. These high yielding conjugate addition pathways deliver unprecedented ß-substituted alkenyl sulfonyl fluorides as single isomers with minimal purification, greatly enriching the repertoire of DOC and holding true to the fundamentals of modular click chemistry. Further, we demonstrate the potential for biological function - a key objective of click chemistry - of this family of SASF-derived molecules as covalent inhibitors of human neutrophil elastase.

Lanthanide Inorganic Nanoparticles Enhance Semiconducting Polymer Nanoparticles Afterglow Luminescence for In Vivo Afterglow/Magnetic Resonance Imaging.

Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.

Legumain-Triggered Macrocyclization of Radiofluorinated Tracer for Enhanced PET Imaging.

Enhancing the accumulation and retention of small-molecule probes in tumors is an important way to achieve accurate cancer diagnosis and therapy. Enzyme-stimulated macrocyclization of small molecules possesses great potential for enhanced positron emission tomography (PET) imaging of tumors. Herein, we reported an 18F-labeled radiotracer [18F]AlF-RSM for legumain detection in vivo. The tracer was prepared by a one-step aluminum-fluoride-restrained complexing agent ([18F]AlF-RESCA) method with high radiochemical yield (RCY) (88.35 ± 3.93%) and radiochemical purity (RCP) (>95%). More notably, the tracer can be transformed into a hydrophobic macrocyclic molecule under the joint action of legumain and reductant. Simultaneously, the tracer could target legumain-positive tumors and enhance accumulation and retention in tumors, resulting in the amplification of PET imaging signals. The enhancement of radioactivity enables PET imaging of legumain activity with high specificity. We envision that, by combining this highly efficient 18F-labeled strategy with our intramolecular macrocyclization reaction, a range of radiofluorinated tracers can be designed for tumor PET imaging and early cancer diagnosis in the future.

Synthesis and Evaluation of Glycosyl Luciferins.

Measuring glycosidase activity is important to monitor any aberrations in carbohydrate hydrolase activity, but also for the screening of potential glycosidase inhibitors. To this end, synthetic substrates are needed which provide an enzyme-dependent read-out upon hydrolysis by the glycosidase. Herein, we present two new routes for the synthesis of caged luminescent carbohydrates, which can be used for determining glycosidase activity with a luminescent reporter molecule. The substrates were validated with glycosidase and revealed a clear linear range and enzyme-dependent signal upon the in situ generation of the luciferin moiety from the corresponding nitrile precursors. Besides, we showed that these compounds could directly be synthesized from unprotected glycosyl-α-fluorides in a two-step procedure with yields up to 75 %. The intermediate methyl imidate appeared a key intermediate which also reacted with d-cysteine to give the corresponding d-luciferin substrate rendering this a highly attractive method for synthesizing glycosyl luciferins in good yields.

α-Silylated Diazoalkynes: New Tools for Bioconjugation of Proteins.

α-Silylated diazoalkynes are stabilized diazo compounds that can selectively react with carboxylic residues in buffered aqueous media. In-situ fluoride induced desilylation increases this reactivity, leading to a very fast reaction. Application to the selective functionalization of RNase A, followed by post-functionalization using click chemistry, is described. These new reagents expand the toolbox for native protein modification at carboxylic residues.

Non-enzymatic biosensor based on F,S-doped carbon dots/copper nanoarchitecture applied in the simultaneous electrochemical determination of NADH, dopamine, and uric acid in plasma.

This work presents the synthesis and characterization of an innovative F,S-doped carbon dots/CuONPs hybrid nanostructure obtained by a direct mixture between F,S-doped carbon dots obtained electrochemically and copper nitrate alcoholic solution. The hybrid nanostructures synthesized were characterized by absorption spectroscopy in the Ultraviolet region (UV-vis), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and different electrochemical techniques. The fluoride and sulfur-doped carbon dots/CuONPs nanostructures were used to prepare a non-enzymatic biosensor on a printed carbon electrode, exhibiting excellent electrocatalytic activity for the simultaneous determination of NADH, dopamine, and uric acid in the presence of ascorbic acid with a detection limit of 20, 80, and 400 nmol L-1, respectively. The non-enzymatic biosensors were also used to determine NADH, dopamine, and uric acid in plasma, and they did not suffer significant interference from each other.

Investigating the Mechanism of Aluminum Fluoride Chelation.

Aluminum fluoride (AlF) complexes have been used over the past decade to incorporate [18F]fluoride into large biomolecules in a highly selective fashion by using relatively facile conditions. However, despite their widespread usage, there are a large number of variations in the reaction conditions, without a definitive discussion provided on the mechanism to understand how these changes would alter the end result. Herein, we report a detailed mechanistic investigation of the reaction, using a mixture of theoretical studies, fluorine-19 and fluorine-18 chemistry, and the consequences it has on the efficient clinical translation of AlF-containing imaging agents.

Sulfate Doping Promotes Agglomeration of Calcium Fluoride Crystals.

Calcium salt precipitation is an effective solution to wastewater fluoride pollution. The purity and precipitation efficiency of calcium fluoride is critical for its removal and recovery. This study aimed to reveal the role of coexisting sulfates in the precipitation of calcium fluoride. A low sulfate concentration promoted calcium fluoride precipitation. The size of calcium fluoride-aggregated particle clusters increased from 750 to 2000 nm when the molar ratio of sulfate to fluoride was increased from 0 to 3:100. Sulfate doped in the calcium fluoride crystals neutralized the positive charge of the calcium fluoride. Online atomic force microscopy measurements showed that sulfate reduced the repulsive force between calcium fluoride crystals and increased the adhesion force from 1.62 to 2.46 nN, promoting the agglomeration of calcium fluoride crystals. Sulfate improved the precipitation efficiency of calcium fluoride by promoting agglomeration; however, the purity of calcium fluoride was reduced by doping. Sulfate reduced the induction time of calcium fluoride crystallization and improved the nucleation rate of calcium fluoride. Sulfate should be retained to improve the precipitation of calcium fluoride and to avoid its loss from the effluents. However, it is necessary to separate sulfate from fluoride to obtain high-purity calcium fluoride. Therefore, sulfate concentration regulation in high-fluoride wastewater is key to achieving the efficient removal and recovery of fluoride ions.

Base-free nickel-catalysed decarbonylative Suzuki-Miyaura coupling of acid fluorides.

The Suzuki-Miyaura cross-coupling of organoboron nucleophiles with aryl halide electrophiles is one of the most widely used carbon-carbon bond-forming reactions in organic and medicinal chemistry1,2. A key challenge associated with these transformations is that they generally require the addition of an exogenous base, the role of which is to enable transmetallation between the organoboron nucleophile and the metal catalyst3. This requirement limits the substrate scope of the reaction because the added base promotes competitive decomposition of many organoboron substrates3-5. As such, considerable research has focused on strategies for mitigating base-mediated side reactions6-12. Previous efforts have primarily focused either on designing strategically masked organoboron reagents (to slow base-mediated decomposition)6-8 or on developing highly active palladium precatalysts (to accelerate cross-coupling relative to base-mediated decomposition pathways)10-12. An attractive alternative approach involves identifying combinations of catalyst and electrophile that enable Suzuki-Miyaura-type reactions to proceed without an exogenous base12-14. Here we use this approach to develop a nickel-catalysed coupling of aryl boronic acids with acid fluorides15-17, which are formed in situ from readily available carboxylic acids18-22. This combination of catalyst and electrophile enables a mechanistic manifold in which a 'transmetallation-active' aryl nickel fluoride intermediate is generated directly in the catalytic cycle13,16. As such, this transformation does not require an exogenous base and is applicable to a wide range of base-sensitive boronic acids and biologically active carboxylic acids.

Advances and future perspectives of water defluoridation by adsorption technology: A review.

Fluoride contamination in water sources poses a significant challenge to human health and the environment. In recent years, adsorption technology has emerged as a promising approach for water defluoridation due to its efficiency and cost-effectiveness. This review article comprehensively explores the advances in water defluoridation through adsorption processes. Various adsorbents, including natural and synthetic materials, have been investigated for their efficacy in removing fluoride ions from water. The mechanisms underlying adsorption interactions are elucidated, shedding light on the factors influencing defluoridation efficiency. Moreover, the review outlines the current state of technology, highlighting successful case studies and field applications. Future perspectives in the field of water defluoridation by adsorption are discussed, emphasizing the need for sustainable and scalable solutions. The integration of novel materials, process optimization, and the development of hybrid technologies are proposed as pathways to address existing challenges and enhance the overall efficacy of water defluoridation. This comprehensive assessment of the advances and future directions in adsorption-based water defluoridation provides valuable insights for researchers, policymakers, and practitioners working towards ensuring safe and accessible drinking water for all.

Amendment of Sargassum oligocystum bio-char with MnFe2O4 and lanthanum MOF obtained from PET waste for fluoride removal: A comparative study.

The use of biomass and waste to produce adsorbent reduces the cost of water treatment. The bio-char of Sargassum oligocystum (BCSO) was modified with MnFe2O4 magnetic particles and La-metal organic framework (MOF) to generate an efficient adsorbent (BCSO/MnFe2O4@La-MOF) for fluoride ions (F-) removal from aqueous solutions. The performance of BCSO/MnFe2O4@La-MOF was compared with BCSO/MnFe2O4 and BCSO. The characteristics of the adsorbents were investigated using various techniques, which revealed that the magnetic composites were well-synthesized and exhibited superparamagnetic properties. The maximum adsorption efficiencies (BCSO: 97.84%, BCSO/MnFe2O4: 97.85%, and BCSO/MnFe2O4@La-MOF: 99.36%) were achieved under specific conditions of pH 4, F- concentration of 10 mg/L, and adsorbent dosage of 3, 1.5, and 1 g/L for BCSO, BCSO/MnFe2O4, and BCSO/MnFe2O4@La-MOF, respectively. The results demonstrated that the experimental data adheres to a pseudo-second-order kinetic model. The enthalpy, entropy, and Gibbs free energy were determined to be negative; thus, the F- adsorption was exothermic and spontaneous in the range of 25-50 °C. The equilibrium data of the process exhibited conformity with the Langmuir model. The maximum adsorption capacities of F- ions were determined as 10.267 mg/g for BCSO, 14.903 mg/g for the BCSO/MnFe2O4, and 31.948 mg/g for BCSO/MnFe2O4@La-MOF. The KF and AT values for the F- adsorption were obtained at 21.03 mg/g (L/mg)1/n and 100 × 10+9 L/g, indicating the pronounced affinity of the BCSO/MnFe2O4@La-MOF towards F- than other samples. The significant potential of the BCSO/MnFe2O4@La-MOF magnetic composite for F- removal from industrial wastewater, makes it suitable for repeated utilization in the adsorption process.

Stratified control of chemical crystallization in a pellet fluidized bed for pH-Adjusted fluoride and phosphate reduction: An experimental study.

Chemical crystallization granulation in a fluidized bed offers an environmentally friendly technology with significant promise for fluoride removal. This study investigates the impact of stratified pH control in a crystallization granulation fluidized bed for the removal of fluoride and phosphate on a pilot scale. The results indicate that using dolomite as a seed crystal, employing sodium dihydrogen phosphate (SDP) and calcium chloride as crystallizing agents, and controlling the molar ratio n(F):n(P):n(Ca) = 1:5:10 with an upflow velocity of 7.52 m/h, effectively removes fluoride and phosphate. Stratified pH control-maintaining weakly acidic conditions (pH = 6-7) at the bottom and weakly alkaline conditions (pH = 7-8) at the top-facilitates the induction of fluoroapatite (FAP) and calcium phosphate crystallization. This approach reduces groundwater fluoride levels from 9.5 mg/L to 0.2-0.6 mg/L and phosphate levels to 0.1-0.2 mg/L. Particle size analysis, scanning electron microscopy-energy-dispersive X-ray spectroscopy, and X-ray diffraction physical characterizations reveal significant differences in crystal morphology between the top and bottom layers, with the lower layer primarily generating high-purity FAP crystals. Further analysis shows that dolomite-induced FAP crystallization offers distinct advantages. SDP not only dissolves on the dolomite surface to provide active sites for crystallization but also, under weakly acidic conditions, renders both dolomite and FAP surfaces negatively charged. This allows for the effective adsorption of PO43-, HPO42-, and F- anions onto the crystal surfaces. This study provides supporting data for the removal of fluoride from groundwater through induced FAP crystallization in a chemical crystallization pellet fluidized bed.

A supramolecular fluorescence sensor array for the differentiation of multiple anions and prediction of iodine in artificial urine using machine learning.

The simultaneous discrimination and detection of multiple anions in an aqueous solution has been a major challenge due to their structural similarity and low charge radii. In this study, we have constructed a supramolecular fluorescence sensor array based on three host-guest complexes to distinguish five anions (F-, Cl-, Br-, I-, and ClO-) in an aqueous solution using anionic-induced fluorescence quenching combined with linear discriminant analysis. Due to the different affinities of the three host-guest complexes for each anion the anion quenching efficiency for each host-guest complex was likewise different, and the five anions were well recognized. The fluorescence sensor array not only distinguished anions at different concentrations (0.5, 10, and 50 µM) with 100% accuracy but also showed good linearity within a certain concentration range. The limit of detection (LOD) was < 0.5 µM. Our interference study showed that the developed sensor array had good anti-interference ability. The practicability of the developed sensor array was also verified by the identification and differentiation of toothpaste brands with different fluoride content and the prediction of the iodine concentration in urine combined with machine learning.

Marginal integrity of prototype bioactive glass-doped resin composites in class II cavities.

OBJECTIVES: This in vitro study examined the marginal integrity of experimental composite materials doped with bioactive glass (BG). MATERIALS AND METHODS: Class-II MOD cavities were prepared and restored with one of the following composite materials: a commercial composite material as a reference (Filtek Supreme XTE), an experimental composite doped with BG 45S5 (C-20), and an experimental composite doped with a fluoride-containing BG (F-20). Six experimental groups (n = 8) were used, as each of the three composites was applied with (+) or without (-) a universal adhesive (Adper Scotchbond Multipurpose). All specimens were subjected to thermocycling (10,000 x, 5-55 °C) and then additionally stored in artificial saliva for eight weeks. Scanning electron micrographs of the mesial and the distal box were taken at three time points (initial, after thermocycling, and after eight weeks of storage in artificial saliva). The margins were classified as "continuous" and "non-continuous" and the percentage of continuous margins (PCM) was statistically analyzed (α = 0.05). RESULTS: In most experimental groups, thermocycling led to a significant decrease in PCM, while the additional 8-week aging had no significant effect. F-20 + performed significantly better (p = 0.005) after 8 weeks storage in artificial saliva than the reference material with adhesive, while no statistically significant differences were observed at the other two time points. C-20 + exhibited significantly better PCM than the reference material with adhesive after thermocycling (p = 0.026) and after 8 weeks (p = 0.003). CONCLUSIONS: Overall, the experimental composites with BG showed at least as good marginal adaptation as the commercial reference, with an indication of possible re-sealing of marginal gaps. CLINICAL RELEVANCE: Maintaining or improving the marginal integrity of composite restorations is important to prevent microleakage and its likely consequences such as pulp irritation and secondary caries.

Process Intensification for Enhanced Fluoride Removal and Recovery as Calcium Fluoride Using a Fluidized Bed Reactor.

This study explored the feasibility of fluoride removal from simulated semiconductor industry wastewater and its recovery as calcium fluoride using fluidized bed crystallization. The continuous reactor showed the best performance (>90% fluoride removal and >95% crystallization efficiency) at a calcium-to-fluoride ratio of 0.6 within the first 40 days of continuous operation. The resulting particle size increased by more than double during this time, along with a 36% increase in the seed bed height, indicating the deposition of CaF2 onto the silica seed. The SEM-EDX analysis showed the size and shape of the crystals formed, along with the presence of a high amount of Ca-F ions. The purity of the CaF2 crystals was determined to be 91.1% though ICP-OES analysis. Following the continuous experiment, different process improvement strategies were explored. The addition of an excess amount of calcium resulted in the removal of an additional 6% of the fluoride; however, compared to this single-stage process, a two-stage approach was found to be a better strategy to achieve a low effluent concentration of fluoride. The fluoride removal reached 94% with this two-stage approach under the optimum conditions of 4 + 1 h HRT combinations and a [Ca2+]/[F-] ratio of 0.55 and 0.7 for the two reactors, respectively. CFD simulation showed the impact of the inlet diameter, bottom-angle shape, and width-to-height ratio of the reactor on the mixing inside the reactor and the possibility of further improvement in the reactor performance by optimizing the FBR configuration.