Encapsulation Mechanism Research Articles

Synthesis of core@shell catalysts guided by Tammann temperature

Designing high-performance thermal catalysts with stable catalytic sites is an important challenge. Conventional wisdom holds that strong metal-support interactions can benefit the catalyst performance, but there is a knowledge gap in generalizing this effect across different metals. Here, we have successfully developed a generalizable strong metal-support interaction strategy guided by Tammann temperatures of materials, enabling functional oxide encapsulation of transition metal nanocatalysts. As an illustrative example, Co@BaAl2O4 core@shell is synthesized and tracked in real-time through in-situ microscopy and spectroscopy, revealing an unconventional strong metal-support interaction encapsulation mechanism. Notably, Co@BaAl2O4 exhibits exceptional activity relative to previously reported core@shell catalysts, displaying excellent long-term stability during high-temperature chemical reactions and overcoming the durability and reusability limitations of conventional supported catalysts. This pioneering design and widely applicable approach has been validated to guide the encapsulation of various transition metal nanoparticles for environmental tolerance functionalities, offering great potential to advance energy, catalysis, and environmental fields.

Study on the physical encapsulation mechanism of heavy metals in fly ash carbonation solidification based on synthetic pellets

The physical encapsulation mechanism prevents the leaching of heavy metals by forming calcium carbonate-encapsulated fly ash through the reaction of carbon dioxide and calcium oxide. However, current research in this area primarily involves qualitative analysis, focusing on various methods to enhance the fixation effect of heavy metals. There is a lack of quantitative description regarding how physical encapsulation solidifies heavy metals, and the solidification mechanism of heavy metals is challenging to verify through macroscopic experiments. In this paper, a method for synthesizing small fly ash particles into pellets is proposed to quantitatively study the mechanism of physically encapsulating heavy metals. The data from the carbonation reaction and leaching reaction are fitted using the shrinking core model. The depth of carbonation increases with the lengthening of carbonation time, and the physical encapsulation strengthens the immobilization of heavy metals. The leaching of heavy metals after carbonation can be categorized into three stages based on the shrinking core model: external diffusion, internal diffusion, and chemical reaction control. Synthetic pellets enhance all three stages, especially the external diffusion, which is not detectable with fly ash powder. The fitting results of the experimental data for the carbonation reaction of the enlarged synthetic pellets and the shrinking core model are both above 0.9. This indicates that the primary barrier to leaching of heavy metals is the physical encapsulation formed by the carbonation reaction following the shrinking core model. The physical encapsulation serves as the primary mechanism for the solidification of heavy metals during the carbonation process.

Compact and efficient KEMs over NTRU lattices

The NTRU lattice is a promising candidate to construct practical cryptosystems, in particular key encapsulation mechanism (KEM), resistant to quantum computing attacks. Nevertheless, there are still some inherent obstacles to NTRU-based KEM schemes when considering integrated performance, taking security, bandwidth, error probability, and computational efficiency as a whole, that is as good as and even better than their {R,M}LWE-based counterparts. In this work, we address the challenges by presenting a new family of NTRU-based KEM schemes, denoted as CTRU and CNTR. By bridging low-dimensional lattice codes and high-dimensional NTRU-lattice-based cryptography with careful design and analysis, to the best of our knowledge, CTRU and CNTR are the first NTRU-based KEM schemes featuring scalable ciphertext compression via only one single ciphertext polynomial, and are the first that can outperform {R,M}LWE-based KEM schemes in terms of integrated performance. For instance, when compared to Kyber, the only KEM scheme currently standardized by NIST, our recommended parameter set CNTR-768 exhibits approximately 12% smaller ciphertext size, when its security is strengthened by (8,7) bits for classical and quantum security respectively, with a significantly lower error probability (2−230 for CNTR-768 vs. 2−164 for Kyber-768). In terms of the state-of-the-art AVX2 implementation of Kyber-768, CNTR-768,achieves a speedup of 2.7X in KeyGen, 3.3X in Encaps, and 1.6X in Decaps, respectively. When compared to the NIST Round 3 finalist NTRU-HRSS, CNTR-768,features 15% smaller ciphertext size, coupled with an improvement of (55,49) bits for classical and quantum security respectively. As for the AVX2 implementation, CNTR-768,outperforms NTRU-HRSS by 26X in KeyGen, 3.0X in Encaps, and 2.2X in Decaps, respectively. Along the way, we develop new techniques for more accurate error probability analysis, and a unified number theoretic transform (NTT) implementation for multiple parameter sets, which may be of independent interest.

Cation induced changes to the structure of cryptophane cages.

Here the monocation complexes of seven anti-cryptophanes are examined with high-resolution ion-mobility mass spectrometry. The relative size of the [cation + cryptophane]+ complexes were compared based on their measured mobilities and derived collisional cross sections. A paradoxical trend of structural contraction was observed for complexes of increasing cation size. Density functional theory confirmed encapsulation occurs for cation = Na+, K+, Rb+, Cs+ and NH4+. However, cation = Li+ preferred oxygen coordination at a linker over encapsulation within the cavity, leading to a slightly larger gas phase structure overall. Protonated cryptophanes yielded much larger collision cross sections via imploded cryptophane structures. Thus, competing physical effects led to the observed non-periodic size trend of the complexes. Trends in complexation from isothermal titration calorimetry and other condensed phase techniques were borne out by the gas phase studies. Further, predicted cavity sizes compared with the gas phase experimental findings reveal more about the encapsulation mechanisms themselves.

Unraveling mechanisms of protein encapsulation and release in coacervates via molecular dynamics and machine learning.

Coacervates play a pivotal role in protein-based drug delivery research, yet their drug encapsulation and release mechanisms remain poorly understood. Here, we utilized the Martini model to investigate bovine serum albumin (BSA) protein encapsulation and release within polylysine/polyglutamate (PLys/PGlu) coacervates. Our findings emphasize the importance of ingredient addition sequence in coacervate formation and encapsulation rates, attributed to preference contact between oppositely charged proteins and poly(amino acid)s. Notably, coacervates composed of β-sheet poly(amino acid)s demonstrate greater BSA encapsulation efficiency due to their reduced entropy and flexibility. Furthermore, we examined the pH responsiveness of coacervates, shedding light on the dissolution process driven by Coulomb forces. By leveraging machine learning algorithms to analyze simulation results, our research advances the understanding of coacervate-based drug delivery systems, with the ultimate goal of optimizing therapeutic outcomes.

WEB CLOUD WEB-BASED CLOUD STORAGE FOR SECURE DATA SHARING ACROSS PLATFORMS

With more and more data moving to the cloud, privacy of user data have raised great concerns. Client-side encryption/decryption seems to be an attractive solution to protect data security, however, the existing solutions encountered three major challenges: low security due to encryption with low-entropy PIN, inconvenient data sharing with traditional encryption algorithms, and poor usability with dedicated software/plugins that require certain types of terminals. This work designs and implements WebCloud, a practical browser-side encryption solution, leveraging modern Web technologies. It solves all the above three problems while achieves several additional remarkable features: robust and immediate user revocation, fast data processing with offline encryption and outsourced decryption. Notably, our solution works on any device equipped with a Web user agent, including Web browsers, mobile and PC applications. We implement WebCloud based on ownCloud for basic file management utility, and utilize WebAssembly and Web Cryptography API for complex cryptographic operations integration. Finally, comprehensive experiments are conducted with many well-known browsers, Android and PC applications, which indicates that WebCloud is cross-platform and efficient. As an interesting by-product, the design of WebCloud naturally embodies a dedicated and practical ciphertext-policy attribute-based key encapsulation mechanism (CP-ABKEM) scheme, which can be useful in other applications.

Research on Public Sector Information Resource Management Innovation in the Age of Digital Economy

Abstract As strategic resources, public sector information resources are increasingly in demand in the information society in the era of the digital economy, and their configuration and management have gradually become a hot topic of concern for the government and society. To enhance the management efficiency and information-sharing ability of public sector information resources, a public sector information resource management system is established with the support of information technology. A public sector information resource data encryption transmission scheme is created through the combination of cloud platform technology for integrated management of information resources and a key encapsulation mechanism. The public sector information resource sharing scheduling model is designed with the optimization objective of maximizing the utilization of information resources, and the fireworks optimization algorithm is used to optimize its fitness value function to obtain the optimal information resource sharing scheduling strategy. When the encrypted transmission of public sector information resources is carried out, the probability of information leakage is only 1.28%, and the information protection efficiency is up to 7.88%. The throughput of the sharing model for information resources can be up to 533.78MB, and the communication overhead for sharing information resources is less than 20%. The establishment of a public sector information resource management system based on information technology effectively enhances the management efficiency of information resources in the public sector and promotes the efficient sharing of information resources.

Analysis and comparison of the security of electronic signatures based on new quantum-resistant problems

Due to the development of quantum computers and quantum methods and algorithms, in order to ensure the security of information after the development of cryptographically relevant quantum computers, NIST conducted the NIST PQC competition. As a result of conducting three rounds of NIST PQC, NIST selected 4 candidates for standardization and four candidates for the fourth round (key encapsulation mechanisms BIKE, Classic McEliece, HQC, and SIKE (which the developers considered unreliable)). Due to the fact that selected algorithms are based on the use of lattices and to add diversity to this list through the use of general-purpose signatures, the process of standardizing additional digital signatures for quantum-resistant cryptography has been initiated.
 The following types of signatures are considered for the first round of this standardization process: code-based signatures, isogeny signatures, multivariate signatures, symmetric signatures, MPC-in-the-head, and NIST-defined "other" signatures. These "other" digital signatures are mostly based on new and promising post-quantum (quantum-resistant) problems.
 The purpose of the work is to analyze and compare candidates for quantum-resistant digital signatures, based on new and promising quantum-resistant problems, resistant to classical and quantum attacks and side-channel attacks. The paper provides comparison of four digital signatures classified by NIST as "other", namely: ALTEQ, eMLE-Sig 2.0, KAZ-SIGN, Xifrat1-Sign.I. For this purpose, the paper presents the basic principles of each of these digital signatures, their main parameters and available at the time of consideration attack vectors. The paper also provides unconditional criteria necessary for comparison. Digital signatures were compared according to such unconditional criteria as: possible lengths of the public key, possible lengths of the personal (secret) key, length of the result of cryptographic algorithm; and conclusions are made regarding the completeness of given comparison and the possibility of further research is highlighted.

N-Methyl- and N-Phenylpiperazine Functionalized Styryl Dyes Inside Cucurbiturils: Theoretical Assessment of the Factors Governing the Host-Guest Recognition.

The family of cucurbiturils (CBs), the unique pumpkin-shaped macrocycles, has received great attention over the past four decades owing to their remarkable recognition properties. They have found diverse applications including biosensing and drug delivery technologies. The cucurbituril complexation of guest molecules can modulate their pKas, improve their solubility in aqueous solution, and reduce the adverse effects of the drugs, as well as enhance the stability and/or enable targeted delivery of the drug molecule. Employing twelve cationic styryl dyes with N-methyl- and N-phenylpiperazine functionality as probes, we attempted to understand the factors that govern the host-guest complexation of such molecules within CB[7] and CB[8] host systems. Various key factors determining the process were recognized, such as the pH and dielectric constant of the medium, the cavity size of the host, the chemical characteristics of the substituents in the guest entity, and the presence/absence of metal cations. The presented results add to our understanding (at the molecular level) of the mechanism of encapsulation of styryl dyes by cucurbiturils, thus shedding new light on various aspects of the intriguing complexation chemistry and the underlying recognition processes.

Optimizing Hardware Resource Utilization for Accelerating the NTRU-KEM Algorithm

This paper focuses on enhancing the performance of the Nth-degree truncated-polynomial ring units key encapsulation mechanism (NTRU-KEM) algorithm, which ensures post-quantum resistance in the field of key establishment cryptography. The NTRU-KEM, while robust, suffers from increased storage and computational demands compared to classical cryptography, leading to significant memory and performance overheads. In environments with limited resources, the negative impacts of these overheads are more noticeable, leading researchers to investigate ways to speed up processes while also ensuring they are efficient in terms of area utilization. To address this, our research carefully examines the detailed functions of the NTRU-KEM algorithm, adopting a software/hardware co-design approach. This approach allows for customized computation, adapting to the varying requirements of operational timings and iterations. The key contribution is the development of a novel hardware acceleration technique focused on optimizing bus utilization. This technique enables parallel processing of multiple sub-functions, enhancing the overall efficiency of the system. Furthermore, we introduce a unique integrated register array that significantly reduces the spatial footprint of the design by merging multiple registers within the accelerator. In experiments conducted, the results of our work were found to be remarkable, with a time-area efficiency achieved that surpasses previous work by an average of 25.37 times. This achievement underscores the effectiveness of our optimization in accelerating the NTRU-KEM algorithm.

Enhanced stability of anthocyanins by cyclodextrin–metal organic frameworks: Encapsulation mechanism and application as protecting agent for grape preservation

Anthocyanins are promising naturally occurring food preservatives for enhancing the quality of food products due to their excellent antioxidant properties. However, their low stability hinders their food packaging application. Here, we propose a facile strategy to achieve the improved stability of anthocyanins encapsulated in γ-cyclodextrin metal-organic frameworks (CD-MOFs) with an in-depth exploration of their structure–property relationships. The adsorbed anthocyanins in CD-MOFs are stabilized by multiple cooperative non-covalent interactions including hydrogen bonding and van der Waals (vdW) interactions as demonstrated by density functional theory (DFT) calculations and spectroscopy analysis. Particularly, by ion-exchange of acetate ions into the pores of CD-MOFs, the resulting CD-MOFs (CD-MOF_OAc) shows a higher anthocyanins adsorption rate with a maximum loading capacity of 83.7 % at 1 min. Besides, CD-MOF_OAc possesses the more effective protecting effect on anthocyanins with at least two-fold enhancement of stability in comparison of free anthocyanins under heating and light irradiation. The anthocyanins encapsulated CD-MOFs films for fruit freshness was validated by the Kyoho experiment. This novel encapsulation system provides a new possibility for the potential use of CD-MOFs as the encapsulating material for anthocyanins in fruit preservation.

Polymersomes in Drug Delivery─From Experiment to Computational Modeling.

Polymersomes, composed of amphiphilic block copolymers, are self-assembled vesicles that have gained attention as potential drug delivery systems due to their good biocompatibility, stability, and versatility. Various experimental techniques have been employed to characterize the self-assembly behaviors and properties of polymersomes. However, they have limitations in revealing molecular details and underlying mechanisms. Computational modeling techniques have emerged as powerful tools to complement experimental studies and enabled researchers to examine drug delivery mechanisms at molecular resolution. This review aims to provide a comprehensive overview of the state of the art in the field of polymersome-based drug delivery systems, with an emphasis on insights gained from both experimental and computational studies. Specifically, we focus on polymersome morphologies, self-assembly kinetics, fusion and fission, behaviors in flow, as well as drug encapsulation and release mechanisms. Furthermore, we also identify existing challenges and limitations in this rapidly evolving field and suggest possible directions for future research.

High Throughput Acceleration of Scabbard Key Exchange and Key Encapsulation Mechanism Using Tensor Core on GPU for IoT Applications

High throughput key encapsulations and decapsulations are needed by IoT applications in order to simultaneously process a multitude of small data in secure communication. In this paper, we present two novel techniques for accelerating the implementation of polynomial convolution on a GPU, utilizing advanced Tensor cores, which benefit the performance of key encapsulations. First, a polynomial re-structuring technique is proposed to allow several polynomials with distinct public keys to be processed in a single communication cycle. This is an improvement compared to the previous work by Lee et al. Next, we observe that polynomial convolution in some key encapsulation mechanisms contains reduction patterns that are not friendly to parallel implementation. We propose separating the multiplication and reduction processes so they can be parallelized independently. To verify the effectiveness of our proposed techniques, we applied it to two key-encapsulation mechanisms from the Scabbard post-quantum key-encapsulation mechanism suite and evaluate their performance. Experimental results show that polynomial convolution using Tensor cores is 1.05× faster (for the Florete scheme) and 3.6× faster (for the Sable scheme) than using CUDA core-based multiplication with conventional cores on a GPU. The Tensor cores based encapsulations and decapsulations are faster than a reference implementation on a CPU supporting AVX2 by more than 5.6× and 6.4×, respectively, for the Florete scheme and 8.3× and 13.3× faster, respectively, for the Sable scheme. This shows that the proposed techniques can achieve significantly higher throughput for key exchange and encapsulation mechanisms, which are important for securing IoT applications.

Plant exosome-like nanovesicles derived from sesame leaves as carriers for luteolin delivery: Molecular docking, stability and bioactivity

The growing recognition of luteolin (Lu) as a vital functional component is attributed to its notable bioactive properties. However, the effective use of Lu is hindered by its inherent limitations related to water solubility, stability, and bioavailability. Here, we aim to develop sesame leaves-derived exosome-like nanovesicles (Exo) for Lu delivery (Exo@Lu) as vehicles. The encapsulation mechanism, solubility, stability, and bioactivity of Exo@Lu were thoroughly evaluated. Exo enriched abundant lipids, proteins, and phenolic compounds with an encapsulation efficiency of ∼ 91.9 % and a loading capacity of ∼ 20.5 % for Lu. The primary binding forces responsible for the encapsulation were hydrogen bonds and van der Waals forces. After encapsulation, the water solubility and stability of Lu were significantly improved under various conditions, including thermal, light, storage, ionic strength, and pH. Exo@Lu maintained structural integrity during simulated digestion, enhancing bioaccessibility and efficacy in mitigating oxidative stress and inflammatory response compared to Exo and free Lu.

Surface electronics regulation and enhanced electrochemical performance of nitrogen-doped carbon layer encapsulated NiCo2S4 nanosheets for supercapacitors

The rational construction of nano-architecture and the regulation of surface electronics in active materials are crucial for high-energy supercapacitors. Herein, a nitrogen-doped carbon layer (NC) was encapsulated on the electrodeposited NiCo2S4 nanosheets on nickel foam (NF) via the thermal vapor deposition polymerization technique, which effectively mitigated the volume fluctuation of NiCo2S4 nanosheets and significantly enhanced the electrical conductivity. Additionally, the electronic structure of the carbon skeleton and the adsorption energy of OH− can be tuned by the incorporation of pyridinic-N and pyrrolic-N in the NC, as revealed by density functional theory (DFT) calculations. Consequently, the binder-free NiCo2S4@NC/NF electrode exhibits superior storage capacity (1800 and 1420.5 F/g at 1 and 20 A/g, respectively). Moreover, the assembled hybrid supercapacitor with NiCo2S4@NC/NF as cathode and N-doped activated carbon (N-AC) as anode exhibits high energy density (46.0 Wh/kg) and long-cycling stability (91.4 % retention after 4000 cycles). Our work unveils the mechanism of NC encapsulation in modulating the surface electronic structure, the adsorption energy towards the electrolyte ions and the electrochemical performance of the materials at the theoretical calculation level. This finding provides a promising avenue for engineering the surface electronics in energy storage devices.

Lightweight Privacy-Preserving Distributed Recommender System Using Tag-Based Multikey Fully Homomorphic Data Encapsulation

Recommender systems facilitate personalized service provision through the statistical analysis and model training of user historical data (e.g. user profile based on keyword searches, browsing behavior, travel history, etc). To address the underpinning privacy implications associated with such systems, a number of privacy-preserving recommendation approaches have been presented in the literature. There are, however, limitations in many of these approaches. For example, approaches that apply public key (fully) homomorphic encryption (FHE) on different users' historical rating records under a unique public key (i.e. the public key of a predefined target user requesting recommendation) incur significant computational overheads on resource-constrained local users and may not be scalable. On the other hand, approaches without utilizing public key FHE can neither resist chosen ciphertext attack (CCA), nor be straightforwardly applied to the setting of distributed servers. In this paper, a lightweight privacy-preserving distributed recommender system is proposed. Specifically, we present a new cryptographic primitive (i.e. tag-based multikey fully homomorphic data encapsulation mechanism; TMFH-DEM) designed to achieve CCA security for both input privacy and result privacy. TMFH-DEM enables a set of distributed servers to collaboratively execute efficient privacy-preserving outsourced computation on multiple inputs encrypted under different secret keys from different data owners, without using public key FHE. The authorized receiver can successfully decrypt the plaintext of the function evaluation result. Building on TMFH-DEM, we propose a lightweight privacy-preserving distributed recommender system, which flexibly returns all the recommended items with certain predicted ratings for all target users. Formal security proof shows that our proposal achieves both user historical rating data privacy and recommendation result privacy. Findings from our evaluations demonstrate its practicability in terms of scalability, recommendation accuracy, computational and communication efficiency.

Kyber, Saber, and SK-MLWR Lattice-Based Key Encapsulation Mechanisms Model Checking with Maude

Facing the potential threat raised by quantum computing, a great deal of research from many groups and industrial giants has gone into building public-key post-quantum cryptographic primitives that are resistant to the quantum attackers. Among them, there is a large number of post-quantum key encapsulation mechanisms (KEMs), whose purpose is to provide a secure key exchange, which is a very crucial component in public-key cryptography. This paper presents a formal security analysis of three lattice-based KEMs including Kyber, Saber, and SK-MLWR. We use Maude, a specification language supporting equational and rewriting logic and a high-performance tool equipped with many advanced features, such as a reachability analyzer that can be used as a model checker for invariant properties, to model the three KEMs as state machines. Because they all belong to the class of lattice-based KEMs, they share many common parts in their designs, such as polynomials, vectors, and message exchange patterns. We first model these common parts and combine them into a specification, called base specification. After that, for each of the three KEMs, by extending the base specification, we just need to model some additional parts and the mechanism execution. Once completing the three specifications, we conduct invariant model checkings with the Maude search command, pointing out a similar man-in-the-middle attack. The occurrence of this attack is due to the fact that authentication is not part of the KEMs, and therefore an active attacker can modify all communication between two honest parties.

Evaluation of Encapsulation Potential of Selected Star-Hyperbranched Polyglycidol Architectures: Predictive Molecular Dynamics Simulations and Experimental Validation

Polymers, including non-linear copolymers, have great potential in the development of drug delivery systems with many advantages, but the design requires optimizing polymer–drug interactions. Molecular dynamics (MD) simulations can provide insights into polymer–drug interactions for designing delivery systems, but mimicking formulation processes such as drying is often not included in in silico studies. This study demonstrates an MD approach to model drying of systems comprising either hydrophilic tinidazole or hydrophobic clotrimazole drugs with amphiphilic hyperbranched copolyethers. The simulated drying protocol was critical for elucidating drug encapsulation and binding mechanisms. Experimentally, two polymers were synthesized and shown to encapsulate clotrimazole with up to 83% efficiency, guided by interactions with the hydrophobic core observed in simulations. In contrast, tinidazole is associated with surface regions, indicating capacity differences between drug types. Overall, this work highlights MD simulation of the drying process as an important tool for predicting drug–polymer complex behaviour. The modelled formulation protocol enabled high encapsulation efficiency and opened possibilities for the design of delivery systems based on computationally derived binding mechanisms. This demonstrates a computational–experimental approach where simulated drying was integral to elucidating interactions and developing optimized complexes, emphasizing the value of molecular modelling for the development of drug delivery formulations.

Ultrasound-Assisted Encapsulation of Phytochemicals for Food Applications: A Review.

The use of phytochemicals as natural food additives is a topic of interest for both academic and food industry communities. However, many of these substances are sensitive to environmental conditions. For this reason, encapsulation is usually performed prior to incorporation into food products. In this sense, ultrasound-assisted encapsulation is an emerging technique that has been gaining attention in this field, bringing important advantages for the production of functional food products. This review article covered applications published in the last five years (from 2019 to 2023) on the use of ultrasound to encapsulate phytochemicals for further incorporation into food. The ultrasound mechanisms for encapsulation, its parameters, such as reactor configuration, frequency, and power, and the use of ultrasound technology, along with conventional encapsulation techniques, were all discussed. Additionally, the main challenges of existing methods and future possibilities were discussed. In general, ultrasound-assisted encapsulation has been considered a great tool for the production of smaller capsules with a lower polydispersity index. Encapsulated materials also present a higher bioavailability. However, there is still room for further developments regarding process scale-up for industrial applications. Future studies should also focus on incorporating produced capsules in model food products to further assess their stability and sensory properties.

Mechanism of Fluoride Ion Encapsulation by Magnesium Ions in a Bacterial Riboswitch.

Riboswitches sense various ions in bacteria and activate gene expression to synthesize proteins that help maintain ion homeostasis. The crystal structure of the aptamer domain (AD) of the fluoride riboswitch shows that the F- ion is encapsulated by three Mg2+ ions bound to the ligand-binding domain (LBD) located at the core of the AD. The assembly mechanism of this intricate structure is unknown. To this end, we performed computer simulations using coarse-grained and all-atom RNA models to bridge multiple time scales involved in riboswitch folding and ion binding. We show that F- encapsulation by the Mg2+ ions bound to the riboswitch involves multiple sequential steps. Broadly, two Mg2+ ions initially interact with the phosphate groups of the LBD using water-mediated outer-shell coordination and transition to a direct inner-shell interaction through dehydration to strengthen their interaction with the LBD. We propose that the efficient binding mode of the third Mg2+ and F- is that they form a water-mediated ion pair and bind to the LBD simultaneously to minimize the electrostatic repulsion between three Mg2+ bound to the LBD. The tertiary stacking interactions among the LBD nucleobases alone are insufficient to stabilize the alignment of the phosphate groups to facilitate Mg2+ binding. We show that the stability of the whole assembly is an intricate balance of the interactions among the five phosphate groups, three Mg2+, and the encapsulated F- ion aided by the Mg2+ solvated water. These insights are helpful in the rational design of RNA-based ion sensors and fast-switching logic gates.