Role of size, surface charge, and PEGylated lipids of lipid nanoparticles (LNPs) on intramuscular delivery of mRNA.

Lipid nanoparticles (LNPs) are currently the most commonly used non-viral gene delivery system. Their physiochemical attributes, encompassing size, charge and surface modifications, significantly affect their behaviors both in vivo and in vitro. Nevertheless, the effects of these properties on the transfection and distribution of LNPs after intramuscular injection remain elusive. In this study, LNPs with varying sizes, lipid-based charges and PEGylated lipids were formulated to study their transfection and in vivo distribution. Luciferase mRNA (mLuc) was entraped in LNPs as a model nucleic acid molecule. Results indicated that smaller-sized LNPs and those with neutral potential presented superior transfection efficiency after intramuscular injection. Surprisingly, the sizes and charges did not exert a notable influence on the in vivo distribution of the LNPs. Furthermore, PEGylated lipids with shorter acyl chains contributed to enhanced transfection efficiency due to their superior cellular uptake and lysosomal escape capabilities. Notably, the mechanisms underlying cellular uptake differed among LNPs containing various types of PEGylated lipids, which was primarily attributed to the length of their acyl chain. Together, these insights underscore the pivotal role of nanoparticle characteristics and PEGylated lipids in the intramuscular route. This study not only fills crucial knowledge gaps but also provides significant directions for the effective delivery of mRNA via LNPs.

Unveiling the Composition-Dependent Catalytic Mechanism of Pt-Ni Alloys for Oxygen Reduction: A First-Principles Study.

Unveiling the composition-dependent catalytic mechanism of Pt-based alloy cathodes for the oxygen reduction reaction (ORR) helps improve the proton exchange membrane fuel cells. Using density functional theory calculations, this study investigates the ORR catalytic performance of the Pt-Ni system with various compositions (1.00, ∼0.99, 0.75, 0.50, 0.25, ∼0.01, and 0.00). The ordered solid solution PtNi3(111) system shows activity comparable to Pt(111) and is cost-effective. The Ni1/Pt(111) system, featuring a single Ni atom on the Pt(111) surface as a surface single-atom alloy (SSAA), demonstrates the highest activity with an overpotential of only 0.28, which could be further reduced to 0.21 V by decreasing the surface Ni concentration to 1/16 monolayer coverage. The predicted high activity of Ni1/Pt(111) is confirmed when considering factors such as the implicit solution environment, constant potential conditions, and protonation capability. Moreover, surface-adsorbed oxygen species driven by reaction conditions stabilize these single Ni atoms of Ni1/Pt(111) by preventing segregation and dissolution processes, thereby exhibiting a dual functionality. This study reveals the composition dependence of Pt-based alloys and highlights the stability mechanisms of SSAA catalysts during the ORR.

Technologies for investigating single-molecule chemical reactions.

Single molecules, the smallest independently stable units in the material world, serve as the fundamental building blocks of matter. Among different branches of single-molecule sciences, single-molecule chemical reactions, by revealing the behavior and properties of individual molecules at the molecular scale, are particularly attractive because they can advance the understanding of chemical reaction mechanisms and help to address key scientific problems in broad fields such as physics, chemistry, biology and materials science. This review provides a timely, comprehensive overview of single-molecule chemical reactions based on various technical platforms such as scanning probe microscopy, single-molecule junction, single-molecule nanostructure, single-molecule fluorescence detection and crossed molecular beam. We present multidimensional analyses of single-molecule chemical reactions, offering new perspectives for research in different areas, such as photocatalysis/electrocatalysis, organic reactions, surface reactions and biological reactions. Finally, we discuss the opportunities and challenges in this thriving field of single-molecule chemical reactions.

Magnetic Properties of Self-Assemble Naphthalene Diimide Radical Aggregates.

The concept of creating room-temperature ferromagnets from organic radicals proposed nearly sixty years ago, has recently experienced a resurgence due to advances in organic radical chemistry and materials. However, the lack of definitive design paradigms for achieving stable long-range ferromagnetic coupling between organic radicals presents an uncertain future for this research. Here, an innovative strategy is presented to achieve room-temperature ferromagnets by assembling π-conjugated radicals into π-π stacking aggregates. These aggregates, with ultra-close π-π distances and optimal π-π overlap, provide a platform for strong ferromagnetic (FM) interaction. The planar aromatic naphthalene diimide (NDI) anion radicals form nanorod aggregates with a π-π distance of just 3.26 Å, shorter than typical van der Waals distances. The suppressed electron paramagnetic resonance (EPR) signal and emergent near-infrared (NIR) absorption of the aggregates confirm strong interactions between the radicals. Magnetic measurements of NDI anion radical aggregates demonstrate room-temperature ferromagnetism with a saturated magnetization of 1.1 emu g-1, the highest among pure organic ferromagnets. Theoretical calculations reveal that π-stacks of NDI anion radicals with specific interlayer translational slippage favor ferromagnetic coupling over antiferromagnetic coupling.

Ternary Bi2WO6/TiO2-Pt Heterojunction Sonosensitizers for Boosting Sonodynamic Therapy.

Engineering Z-scheme heterojunctions represents a promising strategy for optimizing the separation and migration of charge carriers in semiconductor sonosensitizers for enhanced reactive oxygen species (ROS) generation. Nevertheless, establishing a continuous and directional pathway for ultrasonic-induced charge flow in Z-scheme heterojunctions remains a significant challenge. In this study, we present a ternary Bi2WO6/TiO2-Pt heterojunction sonosensitizer achieved through the precise growth of Pt nanocrystals on a directionally assembled Bi2WO6/TiO2 Z-scheme structure. The construction of the Bi2WO6/TiO2-Pt heterojunction involves directional growth of Bi2WO6 in situ on the highly exposed (001) crystal facet of TiO2 nanosheets, followed by the precise deposition of nano Pt on the edge (101) crystal facet. The Z-scheme Bi2WO6/TiO2 in the ternary heterojunction ensures effective electron separation, while the Schottky TiO2-Pt interface establishes a well-defined charge flow path and robust redox capabilities. Moreover, nano Pt confers the Bi2WO6/TiO2-Pt heterojunction with excellent peroxidase-mimic and catalase-mimic activities, facilitating interactions with endogenous H2O2 to produce the hydroxyl radicals and O2. It effectively alleviates tumor hypoxia and enhances ROS production. This results in significantly higher efficiency in sonodynamically induced ROS generation compared to pure TiO2 or binary Bi2WO6/TiO2 heterojunctions, as confirmed by DFT theoretical calculation and experiments with both in vitro and in vivo anticancer performance. This study offers valuable insights for designing high-performance Z-scheme sonosensitizer systems.

Entropy-increased LiMn2O4-based positive electrodes for fast-charging lithium metal batteries.

Fast-charging, non-aqueous lithium-based batteries are desired for practical applications. In this regard, LiMn2O4 is considered an appealing positive electrode active material because of its favourable ionic diffusivity due to the presence of three-dimensional Li-ion diffusion channels. However, LiMn2O4 exhibits inadequate rate capabilities and rapid structural degradation at high currents. To circumvent these issues, here we introduce quintuple low-valence cations to increase the entropy of LiMn2O4. As a result, the entropy-increased LiMn2O4-based material, i.e., LiMn1.9Cu0.02Mg0.02Fe0.02Zn0.02Ni0.02O4, when tested in non-aqueous lithium metal coin cell configuration, enable 1000 cell cycles at 1.48 A g-1 (corresponding to a cell charging time of 4 minutes) and 25°C with a discharge capacity retention of about 80%. We demonstrate that the increased entropy in LiMn2O4 leads to an increase in the disordering of dopant cations and a contracted local structure, where the enlarged LiO4 space and enhanced Mn-O covalency improve the Li-ion transport and stabilize the diffusion channels. We also prove that stress caused by cycling at a high cell state of charge is relieved through elastic deformation via a solid-solution transition, thus avoiding structural degradation upon prolonged cycling.

Realizing altermagnetism in two-dimensional metal-organic framework semiconductors with electric-field-controlled anisotropic spin current.

Altermagnets exhibit momentum-dependent spin-splitting in a collinear antiferromagnetic order due to their peculiar crystallographic and magnetic symmetry, resulting in the creation of spin currents with light elements. Here, we report two two-dimensional (2D) metal-organic framework (MOF) semiconductors, M(pyz)2 (M = Ca and Sr, pyz = pyrazine), which exhibit both altermagnetism and topological nodal point and line by using first-principles calculations and group theory. The altermagnetic 2D MOFs exhibit unconventional spin-splitting and macroscopic zero magnetization caused by 4-fold rotation in crystalline real space and 2-fold rotation in spin space, leading to the generation and control of anisotropic spin currents when an in-plane electric field ( E ) is applied. In particular, pure spin current with the spin Hall effect occurs when E is applied along the angular bisector of the two spin arrangements. Our work indicates the existence of altermagnetic MOF systems and a universal approach to generate electric-field-controlled spin currents for potential applications in antiferromagnetic spintronics.

Steering the Orbital Hybridization to Boost the Redox Kinetics for Efficient Li-CO2 Batteries.

The sluggish CO2 reduction and evolution reaction kinetics are thorny problems for developing high-performance Li-CO2 batteries. For the complicated multiphase reactions and multielectron transfer processes in Li-CO2 batteries, exploring efficient cathode catalysts and understanding the interplay between structure and activity are crucial to couple with these pendent challenges. In this work, we applied the CoS as a model catalyst and adjusted its electronic structure by introducing sulfur vacancies to optimize the d-band and p-band centers, which steer the orbital hybridization and boost the redox kinetics between Li and CO2, thus improving the discharge platform of Li-CO2 batteries and altering the deposition behavior of discharge products. As a result, a highly efficient bidirectional catalyst exhibits an ultrasmall overpotential of 0.62 V and a high energy efficiency of 82.8% and circulates stably for nearly 600 h. Meanwhile, density functional theory calculations and multiphysics simulations further elucidate the mechanism of bidirectional activity. This work not only provides a proof of concept to design a remarkably efficient catalyst but also sheds light on promoting the reversible Li-CO2 reaction by tailoring the electronic structure.

Transformer-Based Neural-Network Quantum State Method for Electronic Band Structures of Real Solids.

Recent advancements in neural networks have led to significant progress in addressing many-body electron correlations in small molecules and various physical models. In this work, we propose QiankunNet-Solid, which incorporates periodic boundary conditions into the neural network quantum state (NNQS) framework based on generative Transformer architecture along with a batched autoregressive sampling (BAS) method, enabling the effective ab initio calculation of real solid materials. The accuracy of this method is demonstrated in one-, two-, and three-dimensional periodic systems, with results comparable to those of full configuration interaction and coupled-cluster method, even in the strongly correlated regime. Furthermore, we compute the band structures and density of states for silicon crystal. The successful incorporation of periodic boundary conditions into the NNQS framework through QiankunNet-Solid opens up new possibilities for the accurate and efficient study of electronic structure properties in solid-state physics.

First-Principles Computational Screening of Two-Dimensional Polar Materials for Photocatalytic Water Splitting.

The band gap constraint of the photocatalyst for overall water splitting limits the utilization of solar energy. A strategy to broaden the range of light absorption is employing a two-dimensional (2D) polar material as photocatalyst, benefiting from the deflection of the energy level due to their intrinsic internal electric field. Here, by using first-principles computational screening, we search for 2D polar semiconductors for photocatalytic water splitting from both ground- and excited-state perspectives. Applying a unique electronic structure model of polar materials, there are 13 photocatalyst candidates for the hydrogen evolution reaction (HER) and 8 candidates for the oxygen evolution reaction (OER) without barrier energies from the perspective of the ground-state free energy variation calculation. In particular, Cu2As4Cl2S3 and Cu2As4Br2S3 can catalyze HER and OER simultaneously, becoming promising photocatalysts for overall water splitting. Furthermore, by combining ground-state band structure calculations with excited-state charge distribution and transfer calculated by linear-response time-dependent density functional theory (LR-TDDFT) and time-dependent ab initio nonadiabatic molecular dynamics (NAMD), respectively, the rationality of the 2D polar material model has been manifested. The intrinsic built-in electric field promotes the separation of charge carriers while suppressing their recombination. Therefore, our computational work provides a high-throughput method to design high-performance photocatalysts for water splitting.

Klebsiella pneumoniae increases invasion in intestinal epithelial cells by disrupting the cytoskeleton.

Klebsiella pneumoniae is an opportunistic pathogen and it can cause human mucosal lesions through the intestine, leading to bacteremia and abscess formation in liver and spleen. Previous studies have shown that K. pneumoniae can enter or cross cells through the intestinal epithelium, but the mechanism is unknown. In this study, we treated the intestinal epithelial cell line Caco-2 with KP1195, a clinically isolated strain with high adhesion and invasion of intestinal epithelial cells. The results showed that the treatment of K. pneumoniae could increase the expression of integrin gene and further disrupt the changes of cytoskeleton. Treating Caco-2 with cytoskeletal inhibitor cytorelaxin D can significantly increase the efficiency of K. pneumoniae invading Caco-2 cells. These data suggest that disruption of the cytoskeleton through integrins may be one of the mechanisms by which K. pneumoniae increases intracellular invasion. This study provides a theoretical basis for further understanding of the mechanism of K. pneumoniae entering intestinal epithelial cells.

Electricity Harvesting from Water Evaporation on Hierarchical Pore Gradient Silica Aerogel-Based Generators.

In this study, the electric energy harvesting capability of the hierarchical pore gradient silica aerogel (HPSA) is demonstrated due to its unique porous structure and inherent hydroxyl groups on the surface. Taking advantage of the positively charged surface of unwashed HPSA credited by the preparation strategy, poly(4-styrene sulfonic acid) (PSS) can be spontaneously adsorbed onto unwashed HPSA and shows gradient distribution due to the pore-gradient structure of HPSA. By virtue of the gradient distribution and the stronger ionization of PSS, PSS-modified HPSA (PSS-HPSA) shows enhanced electricity generation performance from natural water evaporation with an average output voltage of 0.77 V on an individual device. The water evaporation-induced electricity property of PSS-HPSA can be maintained in the presence of a low concentration of salt. The desirable salt resistance capability benefits from the unique 3D hierarchical porous structure of HPSA which ensures rapid water replenishment so as to effectively avoid the salt accumulation. The HPSA-based devices with the advantages of unique porous structure, easy functionalization, good physicochemical stability, good salt resistance capability, and eco-friendliness show great potential as water evaporation-induced electricity generators.

Platinum monolayer dispersed on MXenes for electrocatalyzed hydrogen evolution: a first-principles study.

Maximizing platinum's atomic utilization and understanding the anchoring mechanism between platinum moieties and their supports are crucial for the hydrogen evolution reaction (HER). Using density functional theory, we investigate the catalyst of a Pt monolayer on the two-dimensional Mo2TiC2 substrate (PtML/Mo2TiC2) for the reaction. This Pt monolayer shows a Pt(111)-like pattern, with its Pt-Pt bond elongated by about 0.1 Å compared to Pt(111); charge transfer from Mo2TiC2 to the Pt monolayer leads to significant charge accumulation on Pt. This substantial monolayer metal-support interaction optimizes hydrogen adsorption toward optimal HER activity under both constant charge and potential conditions, making PtML/Mo2TiC2 a promising HER catalyst. Detailed studies reveal that the dominant Volmer-Tafel mechanism in the HER occurs on the 1 monolayer hydrogen-covered PtML/Mo2TiC2 surface. The surface Pourbaix diagram identifies this as the stable surface termination under the electrochemical reaction conditions. These findings provide insights into designing stable, efficient, and low platinum-loaded HER catalysts.

Quantifying the conductivity of a single polyene chain by lifting with an STM tip.

Conjugated polymers are promising candidates for molecular wires in nanoelectronics, with flexibility in mechanics, stability in chemistry and variety in electrical conductivity. Polyene, as a segment of polyacetylene, is a typical conjugated polymer with straightforward structure and wide-range adjustable conductance. To obtain atomic scale understanding of charge transfer in polyene, we have measured the conductance of a single polyene-based molecular chain via lifting it up with scanning tunneling microscopy tip. Different from semiconducting characters in pristine polyene (polyacetylene), high conductance and low decay constant are obtained, along with an electronic state around Fermi level and characteristic vibrational mode. These observed phenomena result from pinned molecular orbital owing to molecule-electrode coupling at the interface, and weakened bond length alternation due to electron-phonon coupling inside single molecular chain. Our findings emphasize the interfacial characteristics in molecular junctions and promising properties of polyene, with single molecular conductance as a vital tool for bringing insights into the design and construction of nanodevices.

Bacterial c-di-GMP triggers metamorphosis of mussel larvae through a STING receptor.

Bacteria induced metamorphosis observed in nearly all marine invertebrates. However, the mechanism of bacteria regulating the larvae-juvenile metamorphosis remains unknown. Here, we test the hypothesis that c-di-GMP, a ubiquitous bacterial second-messenger molecule, directly triggers the mollusc Mytilus coruscus larval metamorphosis via the stimulator of interferon genes (STING) receptor. We determined that the deletion of c-di-GMP synthesis genes resulted in reduced c-di-GMP levels and biofilm-inducing activity on larval metamorphosis, accompanied by alterations in extracellular polymeric substances. Additionally, c-di-GMP extracted from tested varying marine bacteria all exhibited inducing activity on larval metamorphosis. Simultaneously, through pharmacological and molecular experiments, we demonstrated that M. coruscus STING (McSTING) participates in larval metamorphosis by binding with c-di-GMP. Our findings reveal that new role of bacterial c-di-GMP that triggers mussel larval metamorphosis transition, and extend knowledge in the interaction of bacteria and host development in marine ecosystems.

The Role of Nanoparticle Morphology on Enhancing Delivery of Budesonide for Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that affects the gastrointestinal tract. The major hurdles impeding IBD treatment are the low targeting efficiency and short retention time of drugs in IBD sites. Nanoparticles with specific shapes have demonstrated the ability to improve mucus retention and cellular uptake. Herein, mesoporous silica nanoparticles (MSNs) with various morphologies were used to deliver budesonide (BUD) for the treatment of IBD. The therapeutic efficacy is strongly dependent on their shapes. The system comprises different shapes of MSNs as carriers for budesonide (BUD), along with Eudragit S100 as the enteric release shell. The encapsulation of Eudragit S100 not only improved the stability of MSNs-BUD in the gastrointestinal tract but also conferred pH-responsive drug release properties. Then, MSNs efficiently deliver BUD to the colon site, and the special shape of MSNs plays a critical role in enhancing their permeability and retention in the mucus layer. Among them, dendritic MSNs (MSND) effectively reduced myeloperoxidase (MPO) activity and levels of inflammatory cytokines in the colon due to long retention time and rapid release in IBD sites, thereby enhancing the therapeutic efficacy against colitis. Given the special shapes of MSNs and pH-responsivity of Eudragit S100, BUD loaded in the voids of MSND (E@MSNs-BUD) could penetrate the mucous layer and be accurately delivered to the colon with minor side effects. This system is expected to complement current treatment strategies for the IBD.

Effective in vivo reactivation of HIV-1 latency reservoir via oral administration of EK-16A-SNEDDS.

The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The "shock and kill" strategy has emerged as a promising approach for clearing HIV latent reservoirs. However, current latency-reversing agents (LRAs) have limitations in effectively and safely activating the latent virus and reducing the HIV latent reservoirs in clinical practice. Previously, EK-16A was extracted from Euphorbia kansui, which had the effect of interfering with the HIV-1 latent reservoir and inhibiting HIV-1 entry. Nevertheless, there is no suitable and efficient EK-16A oral formulation for in vivo delivery and clinical use. In this study, an oral EK-16A self-nanoemulsifying drug delivery system (EK-16A-SNEDDS) was proposed to "shock" the HIV-1 latent reservoir. This system aims to enhance the bioavailability and delivery of EK-16A to various organs. The composition of EK-16A-SNEDDS was optimized through self-emulsifying grading and ternary phase diagram tests. Cell models, pharmacokinetic experiments, and pharmacodynamics in HIV-1 latent cell transplant animal models suggested that EK-16A-SNEDDS could be absorbed by the gastrointestinal tract and enter the blood circulation after oral administration, thereby reaching various organs to activate latent HIV-1. The prepared EK-16A-SNEDDS demonstrated safety and efficacy, exhibited high clinical experimental potential, and may be a promising oral preparation for eliminating HIV-1 latent reservoirs.

High-Throughput Computational Screening of Novel Two-Dimensional Covalent Organic Frameworks for Efficient Photocatalytic Overall Water Splitting.

The pursuit of efficient photocatalysts toward photocatalytic water splitting has attracted wide attention. However, the low efficiency of photocatalytic reactions due to the rapid electron-hole recombination and the time-consuming searching process hinder the development of high-performance photocatalysts. Here, we proposed a data-driven screening procedure for covalent organic frameworks (COFs) as overall solar water-splitting photocatalysts. Based on a COF database through assembling different Cores and Linkers, three COFs are predicted to be efficient photocatalysts for overall solar water splitting after high-throughput computational screening. We found that the photogenerated electrons and holes are well separated on single COF photocatalysts without material engineering, and both hydrogen and oxygen evolution reactions can occur spontaneously on the three screened COFs under visible light radiation. This kind of novel COF screened by a data-driven screening procedure offers new perspectives for advancing efficient photocatalysts.

A DNA tetrahedron-based nanosuit for efficient delivery of amifostine and multi-organ radioprotection.

Unnecessary exposure to ionizing radiation (IR) often causes acute and chronic oxidative damages to normal cells and organs, leading to serious physiological and even life-threatening consequences. Amifostine (AMF) is a validated radioprotectant extensively applied in radiation and chemotherapy medicine, but the short half-life limits its bioavailability and clinical applications, remaining as a great challenge to be addressed. DNA-assembled nanostructures especially the tetrahedral framework nucleic acids (tFNAs) are promising nanocarriers with preeminent biosafety, low biotoxicity, and high transport efficiency. The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity. We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection (tFNAs@AMF, also termed nanosuit). By establishing the mice models of accidental total body irradiation (TBI) and radiotherapy model of Lewis lung cancer, we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress. In the accidental total body irradiation (TBI) mice model, the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase (SOD) activities and malondialdehyde (MDA) contents, and functional recovery of hematopoietic system, reducing IR-induced pathological damages of multi-organ and safeguarding mice from lethal radiation. More importantly, the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer. Based on a conveniently available DNA tetrahedron-based nanocarrier, this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs. Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.

Vertical Dipole Dominates Charge Carrier Lifetime in Monolayer Janus MoSSe.

Two-dimensional semiconductor materials with vertical dipoles are promising photocatalysts as vertical dipoles not only promote the electron-hole separation but also enhance the carrier redox ability. However, the influence of vertical dipoles on carrier recombination in such materials, especially the competing relationship between vertical dipoles and band gaps, is not yet clear. Herein, first-principles calculations and nonadiabatic molecular dynamics simulations were combined to clarify the influence of band gap and vertical dipole on the carrier lifetime in Janus MoSSe monolayer. By comparing with the results of MoS2 and MoSe2 as well as exploring the carrier lifetime of MoSSe under strain regulation, it has been demonstrated that the vertical dipole, rather than the band gap, is the dominant factor affecting the carrier lifetime. Strikingly, a linear relationship between the carrier lifetime and vertical dipole is revealed. These findings have important implications for the design of high-performance photocatalysts and optoelectronic devices.