Effect of terahertz waves on the aggregation behavior of neurotransmitters.

Understanding the dynamics of neurotransmitters is crucial for unraveling synaptic transmission mechanisms in neuroscience. In this study, we investigated the impact of terahertz (THz) waves on the aggregation of four common neurotransmitters through all-atom molecular dynamics (MD) simulations. The simulations revealed enhanced nicotine (NCT) aggregation under 11.05 and 21.44 THz, with a minimal effect at 42.55 THz. Structural analysis further indicated strengthened intermolecular interactions and weakened hydration effects under specific THz stimulation. In addition, enhanced aggregation was observed at stronger field strengths, particularly at 21.44 THz. Furthermore, similar investigations on epinephrine (EPI), 5-hydroxytryptamine (5-HT), and γ-aminobutyric acid (GABA) corroborated these findings. Notably, EPI showed increased aggregation at 19.05 THz, emphasizing the influence of vibrational modes on aggregation. However, 5-HT and GABA, with charged or hydrophilic functional groups, exhibited minimal aggregation under THz stimulation. The present study sheds some light on neurotransmitter responses to THz waves, offering implications for neuroscience and interdisciplinary applications.

Transformable Superisostatic Crystals Self-Assembled from Segment Colloidal Rods.

Transformable mechanical structures can switch between distinct mechanical states. Whether this kind of structure can be self-assembled from simple building blocks at microscale is a question to be answered. In this work, we propose a self-assembly strategy for these structures based on a nematic monolayer of segmented colloidal rods with lateral cutting. By using Monte Carlo simulation, we find that rods with different cutting degrees can self-assemble into different crystals characterized by bond coordination z that varies from 3 to 6. Among these, we identify a transformable superisostatic structure with pgg symmetry and redundant bonds (z = 5). We show that this structure can support either soft bulk modes or soft edge modes depending on its Poisson's ratio, which can be tuned from positive to negative through a uniform soft deformation. We also prove that the bulk soft modes are associated with states of self-stress along the direction of zero strain during uniform soft deformation. The self-assembled transformable structures may act as mechanical metamaterials with potential applications in micromechanical engineering.

Unveiling the multicomponent phase separation through molecular dynamics simulation and graph theory.

Biomolecular condensates formed by multicomponent phase separation play crucial roles in diverse cellular processes. Accurate assessment of individual-molecule contributions to condensate formation and precise characterization of their spatial organization within condensates are crucial for understanding the underlying mechanism of phase separation. Using molecular dynamics simulations and graph theoretical analysis, we demonstrated quantitatively the significant roles of cation-π and π-π interactions mediated by aromatic residues and arginine in the formation of condensates in polypeptide systems. Our findings reveal temperature and chain length-dependent alterations in condensate network parameters, such as the number of condensate network layers, and changes in aggregation and connectivity. Notably, we observe a transition between assortativity and disassortativity in the condensate network. Moreover, polypeptides W, Y, F, and R consistently promote condensate formation, while the contributions of other charged and two polar polypeptides (Q and N) to condensate formation depend on temperature and chain length. Furthermore, polyadenosine and polyguanosine can establish stable connections with aromatic and R polypeptides, resulting in the reduced involvement of K, E, D, Q, and N in phase separation. Overall, this study provides a distinctive, precise, and quantitative approach to characterize the multicomponent phase separation.

Uncovering the Importance of Ligand Mobility on Cellular Uptake of Nanoparticles: Insights from Experimental, Computational, and Theoretical Investigations.

The cellular uptake of nanoparticles (NPs) by biological cells is an important and fundamental process in drug delivery. Previous studies reveal that the physicochemical properties of nanoparticles as well as those of functionalized ligands can both critically affect the uptake behaviors. However, the effect of the conjugation strategy (i.e., the "bond" between the ligand and the NP) on the cellular uptake is overlooked and remains largely elusive. Here, by taking the broadly employed gold nanoparticle as an example, we comprehensively assessed the relationship between the conjugation strategy and uptake behaviors by introducing three ligands with the same functional terminal but different anchoring sites. As revealed by in vitro cell experiments and multiscale molecular simulations, the uptake efficiency of gold NPs was positively correlated with the strength of the "bond" and more specifically the ligand mobility on the NP surface. Moreover, we validated the results presented above by proposing a thermodynamic theory for the wrapping of NPs with mobile ligands. Further, we also showed that the endocytic pathway of NPs was highly dependent on ligand mobility. Overall, this study uncovered a vital role of conjugation strategy in the cellular uptake and may provide useful guidelines for tailoring the biobehaviors of nanoparticles.

Molecular Modeling of the Fluorination Effect on the Penetration of Nanoparticles across Lipid Bilayers.

The fluorinated decorations have recently been widely used in many biomedical applications. However, the potential mechanism of the fluorination effect on the cellular delivery of nanoparticles (NPs) still remains elusive. In this work, we systemically explore the penetration of a perfluoro-octanethiol-coated gold NP (PF-Au NP) and, for comparison, an octanethiol-coated gold NP (OT-Au NP) across lipid bilayers. We also investigated the effect of these two types of NPs on the properties of lipid bilayers. Our findings indicate that the lipid type and the surface tension of the lipid bilayer significantly impact the penetration capabilities of the fluorinated gold NP. By examining the distribution of ligands on the surface of the two types of NPs in water and during the penetration process, we unveil their distinct penetration characteristics. Specifically, the PF-Au NP exhibits amphiphobic behavior (both hydrophobic and lipophobic), while the OT-Au NP exhibits solely hydrophobic characteristics. Finally, we observe that the penetration capabilities can be increased by adjusting the degree of fluorination of the ligands on the NP surface. Overall, this study provides useful physical insights into the unique properties of the fluorinated decorations in NP permeation.

Topology- and size-dependent binding of DNA nanostructures to the DNase I.

The susceptibility of DNA nanomaterials to enzymatic degradation in biological environments is a significant obstacle limiting their broad applications in biomedicine. While DNA nanostructures exhibit some resistance to nuclease degradation, the underlying mechanism of this resistance remains elusive. In this study, the interaction of tetrahedral DNA nanostructures (TDNs) and double-stranded DNA (dsDNA) with DNase I is investigated using all-atom molecular dynamics simulations. Our results indicate that DNase I can effectively bind to all dsDNA molecules, and certain key residues strongly interact with the nucleic bases of DNA. However, the binding of DNase I to TDNs exhibits a non-monotonic behavior based on size; TDN15 and TDN26 interact weakly with DNase I (∼ - 75 kcal/mol), whereas TDN21 forms a strong binding with DNase I (∼ - 110 kcal/mol). Furthermore, the topological properties of the DNA nanostructures are analyzed, and an under-twisting (∼32°) of the DNA helix is observed in TDN15 and TDN26. Importantly, this under-twisting results in an increased width of the minor groove in TDN15 and TDN26, which primarily explains their reduced binding affinity to DNase I comparing to the dsDNA. Overall, this study demonstrated a novel mechanism for local structural control of DNA at the nanoscale by adjusting the twisting induced by length.

Green electrosynthesis of 3,3'-diamino-4,4'-azofurazan energetic materials coupled with energy-efficient hydrogen production over Pt-based catalysts.

The broad employment of clean hydrogen through water electrolysis is restricted by large voltage requirement and energy consumption because of the sluggish anodic oxygen evolution reaction. Here we demonstrate a novel alternative oxidation reaction of green electrosynthesis of valuable 3,3'-diamino-4,4'-azofurazan energetic materials and coupled with hydrogen production. Such a strategy could greatly decrease the hazard from the traditional synthetic condition of 3,3'-diamino-4,4'-azofurazan and achieve low-cell-voltage hydrogen production on WS2/Pt single-atom/nanoparticle catalyst. The assembled two-electrode electrolyzer could reach 10 and 100 mA cm-2 with ultralow cell voltages of 1.26 and 1.55 V and electricity consumption of only 3.01 and 3.70 kWh per m3 of H2 in contrast of the conventional water electrolysis (~5 kWh per m3). Density functional theory calculations combine with experimental design decipher the synergistic effect in WS2/Pt for promoting Volmer-Tafel kinetic rate during alkaline hydrogen evolution reaction, while the oxidative-coupling of starting materials driven by free radical could be the underlying mechanism during the synthesis of 3,3'-diamino-4,4'-azofurazan. This work provides a promising avenue for the concurrent electrosynthesis of energetic materials and low-energy-consumption hydrogen production.

Size Control of On-Surface Self-Assembled Nanochains Using Soft Building Blocks.

Owing to their conformational flexibility, soft molecules with side chains play a crucial role in molecular self-assembly or self-organization processes toward bottom-up building of supramolecular nanostructures. However, the influence of the rotating side chains in the confined space and subsequent surface-confined supramolecular self-assembly remains rarely explored. Herein, using the spatial confinement effect between soft building blocks, we realized size control on surface-confined supramolecular coordination self-assembly through the synergy between the repulsive steric hindrance and the attractive chemical interactions. Combining scanning tunneling microscopy with density functional theory calculations and Monte Carlo simulations, we elucidated the effective repulsive force generated by the thermal wiggling motions of the soft building blocks, allowing length tuning of the self-assembled chain structures. Through a delicate balance between the repulsive interaction induced by the spatial confinement effect and the coordinate chemical interaction, we provide a new strategy for controlling the geometry of the on-surface supramolecular nanostructures.

The epidemiology of traumatic brain injuries in the fastest-paced city in China: a retrospective study.

Introduction: Traumatic brain injury (TBI) seriously affects the quality of human health and the prognosis of the patient, but the epidemiological characteristics of TBI can vary among populations. Numerous changes have occurred in the epidemiological characteristics of individuals with TBI in the fast-paced city of Shenzhen, China. However, little is known about these characteristics. This study aimed to investigate the changes in TBI epidemiology, help clinicians improve medical treatment. Methods: In this retrospective cross-sectional analysis, we collected the data of 4,229 patients with TBI admitted to 20 hospitals in Shenzhen in 2017. We collected data on age, gender, cause and severity of the injury, eventual diagnosis, time from injury to admission in a neurosurgery department, and patient outcomes. Two neurosurgeons simultaneously collected the data. We compared these results with a similar study conducted in Shenzhen during the period from 1994 to 2003 to clarify and explain the changes in the epidemiological characteristics of TBI. Results: The majority of respondents were men [2,830 (66.9%)]. The mean age was 32.5 ± 21.4 years. The youngest patient was less than 1 year old, and the oldest patient was 101 years old. A total of 3,947 (93.3%) patients had a favorable outcome, 219 (5.2%) had an unfavorable outcome, and 63 (1.5%) died. The predominant external cause was falls (1,779 [42.1%]); this was the most common cause of TBI in children and older adults. Riders of electric bicycles (423 [29.0%]) were the most vulnerable to traffic accident-related injuries. Time greater than 50 h from injury to admission to a neurosurgical department had a significant effect on prognosis (p < 0.001). Conclusion: The epidemiological characteristics of TBI have changed significantly over the past 20 years. Falls, rather than traffic accidents, were the most common cause of TBI. Further research is needed to devise solutions to decrease the incidence of falls and improve the outcomes of TBI.

Effect of Terahertz Waves on the Structure of the Aß42 Monomer, Dimer, and Protofibril: Insights from Molecular Dynamics Simulations.

Amyloid-ß (Aß) and its assemblies play important roles in the pathogenesis of Alzheimer's disease (AD). Recent studies conducted by experimental and computational researchers have extensively explored the structure, assembly, and influence of biomolecules and cell membranes on Aß. However, the impact of terahertz waves on the structures of Aß monomers and aggregates remains largely unexplored. In this study, we systematically investigate the molecular mechanisms by which terahertz waves affect the structure of the Aß42 monomer, dimer, and tetramer through all-atom molecular dynamics (MD) simulations. Our findings indicate that terahertz waves at a specific frequency (42.55 THz) can enhance intramolecular and intermolecular interactions in the Aß42 monomer and dimer, respectively, by resonating with the symmetric stretching mode of the -COO- groups and the symmetric bending/stretching mode of -CH3 groups. Consequently, the ß-structure content of the Aß42 monomer is greatly increased, and the binding energy between the monomers in the Aß42 dimer is significantly enhanced. Additionally, our observations suggest that terahertz waves can mildly stabilize the structure of tetrameric protofibrils by enhancing the interactions among peripheral peptides. Furthermore, we also investigated the effect of the frequency of terahertz waves on the structure of Aß42. The present study contributes to a better understanding of the impact of external fields on the biobehavior of Aß42 peptides and may shed some light on the potential risks associated with electromagnetic field radiation.

Two Different Ways of Stress Release in Supercoiled DNA Minicircles under DNA Nick.

It is generally believed that DNA nick is an effective way to release stress in supercoiled DNA, resulting from the twisting motion that individual strands rotate around the axis of the DNA helix. Here, we use MD simulations based on the oxDNA model to investigate the relaxation of 336 bp supercoiled minicircular DNA under DNA nick. Our simulations show that stress release, characterized by the abrupt decrease in linking number, may be induced by two types of DNA motion depending on the nick position. Except for the twisting motion, there is a writhing motion, that is, double strands collectively rotating with one plectoneme removal, which may occur in the process of DNA relaxation with the nick position in the loop region. Moreover, the writhing motion is more likely to occur in the DNA with relatively high hardness, such as C-G pairs. Our simulation results uncover the relationship between structural transformation, stress release, and DNA motion during the dynamic process under DNA nick, indicating the influence of nick position on the relaxation of the supercoiled DNA.

Effect of maleylation and denaturation of human serum albumin on its interaction with scavenger receptors.

The specific recognition of serum proteins by scavenger receptors is critical and fundamental in many biological processes. However, the underlying mechanism of scavenger receptor-serum protein interaction remains elusive. In this work, taking scavenger receptors class A1 (SR-A1) as an example, we systematically investigate its interaction with human serum albumin (HSA) at different states through a combination of molecular docking and all-atom molecular dynamics simulations. It is found that native HSA can moderately bind to collagen-like (CL) region or scavenger receptor cysteine-rich (SRCR) region, with both electrostatic (ELE) and van der Waals (VDW) interactions, playing important roles. After maleylation, the binding energy, particularly the ELE energy, between HSA and CL region is significantly enhanced, while the binding energy between HSA and SRCR region remains nearly unchanged. Additionally, we also observe that unfolding of the secondary structures in HSA leads to a larger contact surface area between denatured HSA and CL region, but has little impact on the HSA-SRCR region interaction. Therefore, similar to maleylated HSA, denatured HSA is also more likely to bind to the CL region of SR-A1.

Hematite: A Good Catalyst for the Thermal Decomposition of Energetic Materials and the Application in Nano-Thermite.

Metal oxides (MOs) are of great importance in catalysts, sensor, capacitor and water treatment. Nano-sized MOs have attracted much more attention because of the unique properties, such as surface effect, small size effect and quantum size effect, etc. Hematite, an especially important additive as combustion catalysts, can greatly speed up the thermal decomposition process of energetic materials (EMs) and enhance the combustion performance of propellants. This review concludes the catalytic effect of hematite with different morphology on some EMs such as ammonium perchlorate (AP), cyclotrimethylenetrinitramine (RDX), cyclotetramethylenete-tranitramine (HMX), etc. The method for enhancing the catalytic effect on EMs using hematite-based materials such as perovskite and spinel ferrite materials, making composites with different carbon materials and assembling super-thermite is concluded and their catalytic effects on EMs is also discussed. Therefore, the provided information is helpful for the design, preparation and application of catalysts for EMs.

Dynamics of protein condensates in weak-binding regime.

Weak complementary interactions between proteins and nucleic acids are the main driving forces of intracellular liquid-liquid phase separation. The sticker-spacer model has emerged as a unifying principle for understanding the phase behavior of these multivalent molecules. It remains elusive how specific interactions mediated by stickers contribute to the rheological properties of the liquid condensates. Previous studies have revealed that for strong binding strength ɛ_{b}, the bulk diffusivity D depends on the effective bond lifetime τ, viz., D∝τ^{-1}. Consequently, equal concentrations of the complementary stickers induce a slow down in the dynamics of the condensates D∝e^{-1.5ɛ_{b}}. However, for weak-binding strength, it is expected that the resulting condensates are dynamic, loose network liquids rather than kinetically arrested, compact clusters. We develop a mean-field theory using the thermodynamics of the associative polymers and perform molecular-dynamics simulations based on the sticker-spacer model to study the controlling factors in the structure and dynamics of such condensates in the weak-binding regime. Through scaling analysis, we delineate how the free sticker fraction W_{f} and the bulk diffusivity D decrease with increasing binding energy and find that the internal dynamics of such network liquids are controlled by the free sticker fraction D∝W_{f}∝e^{-0.5ɛ_{b}} rather than the effective bond lifetime. Referred to as the free-sticker-dominated diffusivity, the microscopic slowdown due to a gradual loss of the free stickers affects the viscosity of the condensates as well, with the scaling of the zero-shear viscosity η∝e^{0.5ɛ_{b}}. Therefore, the way of controlling the structure, diffusivity, and viscosity of the condensates through the binding energy can be tested experimentally.

Effect of the Graphene Nanosheet on Functions of the Spike Protein in Open and Closed States: Comparison between SARS-CoV-2 Wild Type and the Omicron Variant.

The spread of coronavirus disease 2019 caused by SARS-CoV-2 and its variants has become a global health crisis. Although there were many attempts to use nanomaterials-based devices to fight against SARS-CoV-2, it still remains elusive as to how the nanomaterials interact with SARS-CoV-2 and affect its biofunctions. Here, taking the graphene nanosheet (GN) as the model nanomaterial, we investigate its interaction with the spike protein in both WT and Omicron by molecular simulations. In the closed state, the GN can insert into the region between the receptor binding domain (RBD) and the N-terminal domain (NTD) in both wild type (WT) and Omicron, which keeps the RBD in the down conformation. In the open state, the GN can hamper the binding of up RBD to ACE2 in WT, but it has little impact on up RBD and, even worse, stimulates the down-to-up transition of down RBDs in Omicron. Moreover, the GN can insert in the vicinity of the fusion peptide in both WT and Omicron and prevents the detachment of S1 from the whole spike protein. The present study reveals the effect of the SARS-CoV-2 variant on the nanomaterial-spike protein interaction, which informs prospective efforts to design functional nanomaterials against SARS-CoV-2.

Synergetic collision and space separation in microfluidic chip for efficient affinity-discriminated molecular selection.

Efficient molecular selection is a prerequisite for generating molecular tools used in diagnosis, pathology, vaccinology, and therapeutics. Selection efficiency is thermodynamically highly dependent on the dissociation equilibrium that can be reached in a single round. Extreme shifting of equilibrium towards dissociation favors the retention of high-affinity ligands over those with lower affinity, thus improving the selection efficiency. We propose to synergize dual effects by deterministic lateral-displacement microfluidics, including the collision-based force effect and the two-dimensional (2D) separation-based concentration effect, to greatly shift the equilibrium. Compared with previous approaches, this system can remove more low- or moderate-affinity ligands and maintain most high-affinity ligands, thereby improving affinity discrimination in selection. This strategy is demonstrated on phage display in both experiment and simulation, and two peptides against tumor markers ephrin type-A receptor 2 (EphA2) and CD71 were obtained with high affinity and specificity within a single round of selection, which offers a promising direction for discovery of robust binding ligands for a wide range of biomedical applications.

Loading of DOX into a tetrahedral DNA nanostructure: the corner does matter.

With the rapid development of nanotechnology, various DNA nanostructures have been synthesized and widely used in drug delivery. However, the underlying mechanisms of drug molecule loading into the DNA nanostructure are still elusive. In this work, we systematically investigate the interactions of a tetrahedral DNA nanostructure (TDN) with the anti-cancer drug doxorubicin (DOX) by combining molecular docking and all-atom molecular dynamics simulations. It is found that there are five possible binding modes in the single TDN-DOX interactions, namely the outside-corner mode, the inside-corner mode, the major-groove mode, the minor-groove mode, and the intercalation mode, where the van der Waals (VDW) interaction and the electrostatic (ELE) interaction dominate in the case of unionized DOX and ionized DOX, respectively. Moreover, with the increase of the DOX number, some of the interaction modes may disappear and the inside-corner mode is the most energy-favorable mode. The present study enhances the molecular understanding of the role of TDN as the drug carrier, which may provide a useful guideline for the future design of DNA nanostructures.

Uncovering the molecular mechanism for dual effect of ATP on phase separation in FUS solution.

Recent studies reported that adenosine triphosphate (ATP) could inhibit and enhance the phase separation in prion-like proteins. The molecular mechanism underlying such a puzzling phenomenon remains elusive. Here, taking the fused in sarcoma (FUS) solution as an example, we comprehensively reveal the underlying mechanism by which ATP regulates phase separation by combining the semiempirical quantum mechanical method, mean-field theory, and molecular simulation. At the microscopic level, ATP acts as a bivalent or trivalent binder; at the macroscopic level, the reentrant phase separation occurs in dilute FUS solutions, resulting from the ATP concentration-dependent binding ability under different conditions. The ATP concentration for dissolving the protein condensates is about 10 mM, agreeing with experimental results. Furthermore, from a dynamic point of view, the effect of ATP on phase separation is also nonmonotonic. This work provides a clear physical description of the microscopic interaction and macroscopic phase diagram of the ATP-modulated phase separation.

Duality, Hidden Symmetry, and Dynamic Isomerism in 2D Hinge Structures.

Recently, a new type of duality was reported in some deformable mechanical networks that exhibit Kramers-like degeneracy in phononic spectrum at the self-dual point. In this work, we clarify the origin of this duality and propose a design principle of 2D self-dual structures with arbitrary complexity. We find that this duality originates from the partial central inversion (PCI) symmetry of the hinge, which belongs to a more general end-fixed scaling transformation. This symmetry gives the structure an extra degree of freedom without modifying its dynamics. This results in dynamic isomers, i.e., dissimilar 2D mechanical structures, either periodic or aperiodic, having identical dynamic modes, based on which we demonstrate a new type of wave guide without reflection or loss. Moreover, the PCI symmetry allows us to design various 2D periodic isostatic networks with hinge duality. At last, by further studying a 2D nonmechanical magnonic system, we show that the duality and the associated hidden symmetry should exist in a broad range of Hamiltonian systems.

A Patient With Large Cavernous Hemangioma in the Cavernous Sinus Straddling the Saddle With Bilateral Optic Nerve Compression.

BACKGROUND: This report describes the removal of a giant cavernous hemangioma while protecting the blood vessels and nerves to the greatest degree of safety, relieving the intracranial space, and relieving the symptoms of the patient. METHODS: Large cavernous hemangioma crossing into the cavernous sinus in a saddle surgery procedure was retrospectively analyzed, summarizing many cross-regional giant cavernous hemangioma treatments. RESULTS: The patient underwent non-en bloc resection of the tumor with rapid removal. The internal carotid artery and adjacent nerves were safely preserved. CONCLUSION: Large cavernous hemangiomas spanning from the cavernous sinus to the area of the butterfly saddle require complete evaluation, and appropriate surgical entry should be selected. With the surgeon having rich surgical experience, the operation can protect the patient's neurological function.