Accessible Surface Research Articles

Ultrafast Rejuvenation of Aged CsPbI3 Quantum Dots and Efficiency Improvement by Sequential 1-Dodecanethiol Post-Treatment Strategy.

Metal halide perovskite CsPbI3 quantum dots (QDs) have sparked widespread research due to their intriguing optoelectronic. However, the CsPbI3 QDs undergo inevitable aging and luminescence quenching caused by the weak binding ability of oleate (OA-)/oleylammonium (OAm+), hindering further practical application. Herein, we have realized ultrafast rejuvenation of the aged CsPbI3 QDs that have lost their photoluminescence performance based on a 1-dodecanethiol (DDT) surface ligand to restore the outstanding red light emission with a high photoluminescence quantum yield (PLQY) from 25 to 90%. Furthermore, CsPbI3 QDs with DDT surface treatment maintain a cubic phase and high PLQY value even after 35 days. The DDT ligands can form a strong bond with Pb2+ and passivate I- ion vacancies, enhancing radiative recombination efficiency and thereby improving the PLQY of the QDs. The stable yet easily accessible surface of the DDT-capped CsPbI3 QDs was successfully employed as white LEDs and exhibited considerable enhanced luminous performance, suggesting promising application in solid-state lighting fields.

Highly Porous Multiwalled Carbon Nanotube-Foam Composite for Batch Adsorption Performances of Dyes.

Treatment of dye pollutants prior to their release into the environment remains a formidable challenge, persisting as a longstanding issue. This study focuses on the development of a multiwalled carbon nanotube-foam (MWCNT-foam) composite through low-temperature chemical fusion (LTFC), resulting in a composite with a remarkably high accessible surface area (>475 m2 g-1). The MWCNT-foam composite exhibits a three-dimensional porous structure and demonstrates a notable affinity for organic dye adsorption. The efficacy of this composite was evaluated against various cationic dyes such as Methylene blue (MB) and Crystal Violet (CV) as well as anionic dyes such as Congo red (CR) and Eriochrome black T (EB), and the composite showed removal rates exceeding 99%. Furthermore, the study delved into the impact of the initial dye concentration, adsorbent dosage, kinetics, and other factors on the performance of the MWCNT-foam composite. The adsorption process achieved equilibrium in 10 min and strongly correlated with the pseudo-second-order kinetic model and Langmuir isotherm. The maximum adsorption capacity of MWCNT-foam for MB, CV, CR, and EB was found to be 168.63, 147.49, 99.50, and 93.11 mg g-1, respectively. In order to showcase the potential of this material for continuous adsorption, a specialized cartridge was designed and employed to treat dye solutions, demonstrating the feasibility of continuous mode adsorption.

Integrating molecular dynamics simulation with small- and wide-angle X-ray scattering to unravel the flexibility, antigen-blocking, and protease-restoring functions in a hindrance-based pro-antibody.

Spatial hindrance-based pro-antibodies (pro-Abs) are engineered antibodies to reduce monoclonal antibodies' (mAbs) on-target toxicity using universal designed blocking segments that mask mAb antigen-binding sites through spatial hindrance. By linking through protease substrates and linkers, these blocking segments can be removed site-specifically. Although many types of blocking segments have been developed, such as coiled-coil and hinge-based Ab locks, the molecular structure of the pro-Ab, particularly the region showing how the blocking fragment blocks the mAb, has not been elucidated by X-ray crystallography or cryo-EM. To achieve maximal effect, a pro-Ab must have high antigen-blocking and protease-restoring efficiencies, but the unclear structure limits its further optimization. Here, we utilized molecular dynamics (MD) simulations to study the dynamic structures of a hinge-based Ab lock pro-Ab, pro-Nivolumab, and validated the simulated structures with small- and wide-angle X-ray scattering (SWAXS). The MD results were closely consistent with SWAXS data (χ2 best-fit = 1.845, χ2 allMD = 3.080). The further analysis shows a pronounced flexibility of the Ab lock (root-mean-square deviation = 10.90 Å), yet it still masks the important antigen-binding residues by 57.3%-88.4%, explaining its 250-folded antigen-blocking efficiency. The introduced protease accessible surface area method affirmed better protease efficiency for light chain (33.03 Å2) over heavy chain (5.06 Å2), which aligns with the experiments. Overall, we developed MD-SWAXS validation method to study the dynamics of flexible blocking segments and introduced methodologies to estimate their antigen-blocking and protease-restoring efficiencies, which would potentially be advancing the clinical applications of any spatial hindrance-based pro-Ab.

On the Theoretical Quantification of Radii of Atoms in Molecules.

Despite the fundamental importance of radii of atoms in molecules for numerous applications in physics and chemistry, comprehensive methods for their theoretical evaluation are still scarce. Here, we present quantum chemistry-based approaches for evaluation of radii of atoms in molecules and assess their robustness by studying the agreement of van der Waals and solvent-excluded surfaces constructed by them with reference molecular surfaces. By studying a large data set of 1235 molecules, it is shown that estimation of radii via effective and free atomic volumes can accurately take the dependence of atomic radii on the chemical environment into account.

3D Porous Graphene Architecture Integrated with Cu2O for Enhanced Electrochemical Sensing Performance.

Construction and functionalization of a 3D graphene architecture are crucial to harness and extend the unique features of graphene and thus essential for its numerous conventional and novel applications. Herein, a 3D honeycomb-patterned porous graphene architecture is constructed through a facile and low-cost self-assembly process and then integrated with Cu2O nanoparticles via a simple electrodeposition procedure. The 3D porous graphene structure is prepared by the breath figure method using a graphene oxide (GO)-based complex in which GO is modified by a surfactant as the casting material. Benefiting from the intercalation of the surfactant between the GO nanosheets and the fabrication of a 3D porous structure, the aggregation inhibition of GO nanosheets and increases in accessible surface area are realized at both nano- and microscales, resulting in good electrochemical performance. Moreover, the deposition of Cu2O nanoparticles can further improve the electrochemical sensing performance of the porous reduced graphene oxide (rGO) structure. Extremely low detection limit (30.72 nM) with a linear range of 0 μM to 30 μM, excellent anti-interference, repeatability, reproducibility, stability, and high accuracy for actual sample testing are shown when the 3D porous Cu2O/rGO film is applied as an electrochemical sensor for DA detection. This work provides not only a superior electrochemical biosensor but also a simple, yet effective and general strategy for the construction and functionalization of a 3D graphene structure.

Architected Carbon Structures for Energy Storage

Carbon materials, owing to their excellent electrical conductivity, tailor-ability, inexpensiveness, and versatility, have been extensively studied as electrode materials for energy storage devices, including batteries and supercapacitors. In this talk, I will discuss how to combine conventional materials/chemical synthesis with 3D printing techniques to develop architected carbon electrode materials for supercapacitors. The capacitance of carbon-based supercapacitor electrodes has remained at a mediocre level between 100 and 200 F/g for decades. Until recently, a new family of carbon materials termed hierarchical porous carbons has pushed the capacitance to new benchmark values beyond 300 F/g and has revitalized the exploration of carbon materials for supercapacitors. We have recently developed some hierarchical porous carbon areogels contain different scales of pores inter-connected together and assembled in hierarchical patterns, through a combination of freeze drying, template, chemical etching and 3D printing. These porous carbons have an open porous structure, providing an extremely large and accessible surface area. They can be used as electric double layer materials that enable ultrafast charging/discharging and retain outstanding capacitive performance even at ultralow temperatures (-70 °C). They can serve as 3D conductive scaffolds/current collectors to support pseudo-capacitive materials with ultrahigh mass loadings. These findings exemplified how to use a deterministic structure to improve the rate capability of supercapacitors and their capacitances at ultrahigh current densities and mass loadings and ultralow temperatures, which are long-standing challenges for SCs.

(Invited) Chemical Kinetic Method for Active-Site Quantification in Fe-N-C Catalysts and Correlation with Molecular Probe and Spectroscopic Site-Counting Methods

Heterogeneous catalysts consisting of iron cations incorporated into nitrogen-doped carbon (“Fe-N-C”) have received extensive attention as leading alternatives to Pt for the electrochemical oxygen reduction reaction (ORR). Fe-N-C catalysts host mononuclear nitrogen-ligated active centers, FeNx, that frequently coexist with agglomerated Fe species. Although FeNx are the dominant active centers for ORR and other electrocatalytic reactions, the relative accuracies of methods to quantify them are still debated. Here, we develop a kinetic probe-reaction approach to quantify FeNx centers and compare it with spectroscopic and molecular probe methods.Model Fe-N-C catalysts were synthesized to contain mononuclear FeNx species at low loadings (0.1–0.4 wt% bulk Fe) on solvent-accessible surfaces using a postsynthetic metalation approach and their Fe speciation was confirmed by low-temperature 57Fe Mössbauer spectroscopy. The initial rate of oxidation of a water-soluble hydroquinone molecule (per gcatalyst) catalyzed by these model materials correlates linearly with their density of FeNx centers, reflecting their intrinsic turnover frequency (TOF) for this reaction. This TOF, in turn, enables the estimation of the active-site density on any other Fe-N-C catalyst through a simple rate measurement. Kinetically determined FeNx site densities are measured on a suite of fourteen Fe-N-C catalysts with diverse synthetic origins and Fe speciation (0.3–8.4 wt% bulk Fe) and are compared with those estimated by low-temperature 57Fe Mössbauer spectroscopy, CO pulse chemisorption, and electrochemical stripping of NO derived from NO2 −. Kinetic quantifications of FeNx centers correlate well with those obtained from the CO pulse chemisorption method and Mössbauer spectroscopy. The broad survey of Fe-N-C materials also reveals the presence of outliers and challenges associated with each site quantification method. The kinetic method developed here does not require pretreatments that may alter active-site distributions nor specialized equipment beyond reaction vessels and standard analytical instrumentation, offering an attractive complementary approach. Figure 1

Discovery of novel Trichoderma-based bioactive compounds for controlling potato virus Y based on molecular docking and molecular dynamics simulation techniques

BackgroundAlthough potato virus Y (PVY) is the most serious virus-infecting potato plants worldwide, the losses concurred by it remain unmanageable due to the lack of efficient anti-PVY agents. Hence, the objective of this study was to assess the antiviral properties of secondary metabolite compounds obtained from culture filtrates of four Trichoderma spp. isolates. The assessment was conducted using computational methods, including molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, as well as molecular dynamics simulations. The aim was to develop novel and effective agents for combating PVY.ResultsThe GC–MS analysis of the studied Trichoderma spp. secondary metabolites revealed 24 compounds with relative amounts exceeding 10%. Molecular docking was then performed using MOE software to evaluate the activity of these compounds against the PVY protein coat (PDB-ID: 6HXX). Ningnanmycin and ribavirin, known plant virus inhibitors, were employed as reference ligands for comparison. Among the compounds tested, C9, C10, C13, and C19 exhibited superior docking scores, root mean square deviation (RMSD) values, and binding modes compared to the reference ligands. In addition, these compounds successfully passed the ADMET analysis. Further investigation focused on compounds C13 and C19, which underwent in-depth analysis through MDs for 100 ns. The MDs trajectories demonstrated that both complexes exhibited favorable stability, compactness, and binding modes throughout the simulation period. However, the C19/PVY-CP complex outperformed the C13 complex in all calculated parameters such as RMSD, root mean square fluctuation (RMSF), radius of gyration (RoG), solvent-accessible surface area (SASA), and intermolecular hydrogen bonds. Interestingly, these findings aligned with the results obtained from the docking analysis, indicating that C9 and C10 possess high potential against PVY, as they exhibited binding modes like that of C19.ConclusionThese promising outcomes provide a solid foundation for considering the potential use of compounds C9, C10, C13, and C19 as antiviral agents. Further experimental validation and in-depth studies are warranted to assess the efficacy and safety of these compounds and their potential as antiviral therapeutics. To our knowledge, this is the first report to study the biological activities of the Trichoderma-based bioactive compounds against PVY using computational techniques.Graphical abstract

Insilico assessment of hesperidin on SARS-CoV-2 main protease and RNA polymerase: Molecular docking and dynamics simulation approach

The present study uses molecular docking and dynamic simulations to evaluate the inhibitory effect of flavonoid glycosides-based compounds on coronavirus Main protease (Mpro) and RNA polymerase. The Molegro Virtual Docker (MVD) software is utilized to simulate and calculate the binding parameters of compounds with coronavirus. The docking results show that the selected herbal compounds are more effective than those of chemical compounds. It is also revealed that five herbal ligands and two chemical ligands have the best docking scores. Furthermore, a Molecular Dynamics (MD) simulation was conducted for Hesperidin, confirming docking results. Analysis based on different parameters such as Root-mean-square deviation (RMSD), Root mean square fluctuation (RMSF), Radius of gyration (Rg), Solvent accessibility surface area (SASA), and the total number of hydrogen bonds suggests that Hesperidin formed a stable complex with Mpro. Absorption, Distribution, Metabolism, Excretion, And Toxicity (ADMET) analysis was performed to compare Hesperidin and Grazoprevir as potential antiviral medicines, evaluating both herbal and chemical ligand results. According to the study, herbal compounds could be effective on coronavirus and are admissible candidates for developing potential operative anti-viral medicines. Hesperidin was found to be the most acceptable interaction. Grazoprevir is an encouraging candidate for drug development and clinical trials, with the potential to become a highly effective Mpro inhibitor. Compared to RNA polymerase, Mpro showed a greater affinity for bonding with Hesperidin. van der Waals and electrostatic energies dominated, creating a stable Hesperidin-Mpro and Hesperidin-RNA polymerase complex.

Solvent accessible surface area-assessed molecular basis of osmolyte-induced protein stability.

In solvent-modulated protein folding, under certain physiological conditions, an equilibrium exists between the unfolded and folded states of the protein without any need to break or make a covalent bond. In this process, interactions between various protein groups (peptides) and solvent molecules are known to play a major role in determining the directionality of the chemical reaction. However, an understanding of the mechanism of action of the co(solvent) by a generic theoretical underpinning is lacking. In this study, a generic solvation model is developed based on statistical mechanics and the thermodynamic transfer free energy model by considering the microenvironment polarity of the interacting co(solvent)-protein system. According to this model, polarity and the fractional solvent-accessible surface areas contribute to the interaction energies. The present model includes various orientations of participating interactant solvent surfaces of suitable areas. As model systems, besides the backbone we consider naturally occurring amino acid residues solvated in ten different osmolytes, small organic compounds known to modulate protein stability. The present model is able to predict the correct trend of the osmolyte-peptide interactions ranging from stabilizing to destabilizing not only for the backbone but also for side chains. Our model predicts Asn, Gln, Asp, Glu, Arg and Pro to be highly stable in most of the protecting osmolytes while Ala, Val, Ile, Leu, Thr, Met, Lys, Phe, Trp and Tyr are predicted to be moderately stable, and Ser, Cys and Histidine are predicted to be least stable. However, in denaturing solvents, both backbone and side chain models show similar stabilities in urea and guanidine. One of the important aspects of this model is that it is essentially parameter-free and consistent with the electrostatics of the interaction partners that make this model suitable for estimating any solute-solvent interaction energies.

Streamlining NMR Chemical Shift Predictions for Intrinsically Disordered Proteins: Design of Ensembles with Dimensionality Reduction and Clustering.

By merging advanced dimensionality reduction (DR) and clustering algorithm (CA) techniques, our study advances the sampling procedure for predicting NMR chemical shifts (CS) in intrinsically disordered proteins (IDPs), making a significant leap forward in the field of protein analysis/modeling. We enhance NMR CS sampling by generating clustered ensembles that accurately reflect the different properties and phenomena encapsulated by the IDP trajectories. This investigation critically assessed different rapid CS predictors, both neural network (e.g., Sparta+ and ShiftX2) and database-driven (ProCS-15), and highlighted the need for more advanced quantum calculations and the subsequent need for more tractable-sized conformational ensembles. Although neural network CS predictors outperformed ProCS-15 for all atoms, all tools showed poor agreement with HN CSs, and the neural network CS predictors were unable to capture the influence of phosphorylated residues, highly relevant for IDPs. This study also addressed the limitations of using direct clustering with collective variables, such as the widespread implementation of the GROMOS algorithm. Clustered ensembles (CEs) produced by this algorithm showed poor performance with chemical shifts compared to sequential ensembles (SEs) of similar size. Instead, we implement a multiscale DR and CA approach and explore the challenges and limitations of applying these algorithms to obtain more robust and tractable CEs. The novel feature of this investigation is the use of solvent-accessible surface area (SASA) as one of the fingerprints for DR alongside previously investigated α carbon distance/angles or ϕ/ψ dihedral angles. The ensembles produced with SASA tSNE DR produced CEs better aligned with the experimental CS of between 0.17 and 0.36 r2 (0.18-0.26 ppm) depending on the system and replicate. Furthermore, this technique produced CEs with better agreement than traditional SEs in 85.7% of all ensemble sizes. This study investigates the quality of ensembles produced based on different input features, comparing latent spaces produced by linear vs nonlinear DR techniques and a novel integrated silhouette score scanning protocol for tSNE DR.

Impact of surface-active ionic solutions on the structure and function of laccase from trametes versicolor: Insights from molecular dynamics simulations

Many protein-ionic liquid investigations have examined laccase interactions. Laccases are a class of poly-copper oxidoreductases that retain significant biotechnological relevance owing to their notable oxidative capabilities and their application in the elimination of synthetic dyes, phenolic compounds, insecticides, and various other substances. This study investigates the impact of surface active ionic liquids (SAILs), namely, decyltrimethylammonium bromide [N10111][Br] and 1-decyl-3-methylimidazolium chloride [C10mim][Cl] as cationic surfactant ionic liquids and cholinium decanoate [Chl][Dec], an anionic surfactant ionic liquid, on the structure and function of laccase from the fungus Trametes versicolor (TvL) by the molecular dynamics (MD) simulation method. In summary, this study showed that laccase solvent-accessible surface area increased in the ionic liquid [Chl][Dec] while it decreased in the other two ionic liquids. Interestingly, [Chl][Dec] ionic liquid components formed hydrogen bonds with laccase, while [N10111][Br] and [C10mim][Cl] components were unable to form hydrogen bonds with laccase. The quantity of hydrogen bonds formed between water molecules and the enzyme was also diminished in the presence of [Chl][Dec] in comparison to the other two ionic liquids. especially at a concentration of 250 mM. In 250 mM concentrations of [N10111][Br] and [C10mim][Cl], clusters of long-chain cations are likely to form near the copper T1 site. However, even at low [Chl][Dec] concentrations, long [Dec]- chains were observed to penetrate the enzyme near the copper T1 site, and at 250 mM [Chl][Dec], a large cluster of anions occupied the opening of the active site. The results of the analysis also show that the interaction between the [Dec]- anion and the enzyme is stronger than the interaction between [N10111]+ and [C10mim]+ with laccase; in addition, the [Dec]- anion, compared to [Br]- and [Cl]- has a much greater tendency to bind with the enzyme residues.

Antibacterial Efficacy of Hiora: An Ayurvedic Mouthwash in Children.

Mouthwashes, as a form of antimicrobial delivery system, rank among the safest and most effective vehicles, particularly in the case of young children. This is attributed to their ability to distribute therapeutic components across all accessible oral surfaces, including interproximal areas. To evaluate the antibacterial efficacy of recently introduced Ayurvedic (Hiora) and triclosan-based mouthwashes among children. A total of 45 healthy children aged 10-15 years were randomly assigned to three groups: Herbal mouthwash (Hiora), triclosan-based mouthwash (Kidodent), and normal saline as the control group. Saliva samples were collected pre-rinse, 2 minutes, 30 minutes, and 60 minutes post-rinsing with the study mouthwashes. These samples were then inoculated onto Petri dishes containing blood agar culture media, followed by incubation under both aerobic and anaerobic conditions at 37°C for 48 hours. The resulting bacterial colonies of Streptococcus spp. and Lactobacillus spp. were counted (CFU/ml x 105). Statistical analysis, including ANOVA, Newman Keul's Post-hoc test, and a two-tailed 't' test, was conducted to determine the significance of the results. The Ayurvedic Hiora mouthwash demonstrated the most substantial reduction in salivary bacterial colony counts of Streptococcus spp. and Lactobacillus spp. with statistically significant results (p<0.01). The Ayurvedic Hiora mouthwash exhibited the highest antibacterial effectiveness, followed by the triclosan-based mouthwash in decreasing order, with saline showing the least efficacy.

Therapeutic Path to Triple Knockout: Investigating the Pan-inhibitory Mechanisms of AKT, CDK9, and TNKS2 by a Novel 2-phenylquinazolinone Derivative in Cancer Therapy- An In-silico Investigation Therapy.

Blocking the oncogenic Wnt//β-catenin pathway has of late been investigated as a viable therapeutic approach in the treatment of cancer. This involves the multi-targeting of certain members of the tankyrase-kinase family; Tankyrase 2 (TNKS2), Protein Kinase B (AKT), and Cyclin- Dependent Kinase 9 (CDK9), which propagate the oncogenic Wnt/β-catenin signalling pathway. During a recent investigation, the pharmacological activity of 2-(4-aminophenyl)-7-chloro- 3H-quinazolin-4-one was repurposed to serve as a 'triple-target' inhibitor of TNKS2, AKT and CDK9. Yet, the molecular mechanism that surrounds its multi-targeting activity remains unanswered. As such, this study aims to explore the pan-inhibitory mechanism of 2-(4-aminophenyl)-7-chloro-3H-quinazolin- 4-one towards AKT, CDK9, and TNKS2, using in silico techniques. Results revealed favourable binding affinities of -34.17 kcal/mol, -28.74 kcal/mol, and -27.30 kcal/mol for 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one towards TNKS2, CDK9, and AKT, respectively. Pan-inhibitory binding of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one is illustrated by close interaction with specific residues on tankyrase-kinase. Structurally, 2-(4-aminophenyl)-7-chloro- 3H-quinazolin-4-one had an impact on the flexibility, solvent-accessible surface area, and stability of all three proteins, which was illustrated by numerous modifications observed in the unbound as well as the bound states of the structures, which evidenced the disruption of their biological function. Prediction of the pharmacokinetics and physicochemical properties of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4- one further established its inhibitory potential, evidenced by the favourable absorption, metabolism, excretion, and minimal toxicity properties. The following structural insights provide a starting point for understanding the paninhibitory activity of 2-(4-aminophenyl)-7-chloro-3H-quinazolin-4-one. Determining the criticality of the interactions that exist between the pyrimidine ring and catalytic residues could offer insight into the structure-based design of innovative tankyrase-kinase inhibitors with enhanced therapeutic effects.

Spermine and spermidine SI-PPCs: Molecular dynamics reveals enhanced biomolecular interactions

In this paper the effects on the interaction of highly positively charged substitution-inert platinum polynuclear complexes (SI-PPCs) with negatively charged DNA and heparin are examined and compared by theoretical chemistry methods. Electrostatic and hydrogen bonding interactions contribute to the overall effects on the biomolecule. Root Mean Square (RMS) deviation, Solvent Accessible Surface, RMS fluctuation, and interaction analysis all confirm similar effects on both biomolecules, dictated predominantly by the total positive charge and total number of hydrogen bonds formed. Especially, changes in structural parameters suggesting condensation and reduction of available surface area will reduce or prevent normal protein recognition and may thus potentially inhibit biological mechanisms related to apoptosis (DNA) or reduced vascularization viability (HEP). Thermodynamic analyses supported these findings with favourable interaction energies. The comparison of DNA and heparin confirms the general intersectionality between the two biomolecules and confirms the intrinsic dual-nature function of this chemotype. The distinction between the two-limiting mode of actions (HS or DNA-centred) could reflect an intriguing balance between extracellular (GAG) and intracellular (DNA) binding and affinities. The results underline the need to fully understand GAG-small molecule interactions and their contribution to drug pharmacology and related therapeutic modalities. This report contributes to that understanding.

Enhancing and sustaining arsenic removal in a zerovalent iron-based magnetic flow-through water treatment system

In areas affected by arsenicosis, zerovalent iron (ZVI)/sand filters are extensively used by households to treat groundwater, but ZVI surface passivation and filter clogging limit their arsenic (As) removal performance. Here we present a magnetic confinement-enabled column reactor coupled with periodic ultrasonic depassivation (MCCR-PUD), which efficiently and sustainably removes As by reaction with continuously generated iron (oxyhydr)oxides from ZVI oxidative corrosion. In the MCCR, ZVI microparticles self-assemble into stable millimeter-scale wires in forest-like arrays in a parallel magnetic field (0.42−0.48 T, produced by two parallel permanent magnets), forming a highly porous structure (87 % porosity) with twice the accessible reactive surface area of a ZVI/sand mixture. For a feed concentration of 100 μg/L As(III), the MCCR-PUD, with a short empty bed contact time (1.6 min), treated ca. 7340 empty bed volume (EBV) of water at breakthrough (10 μg/L), 9.4 folds higher than that of a ZVI/sand filter. Due to the large interspace between ZVI wires, the MCCR-PUD effectively prevented column clogging that occurred in the ZVI/sand filter. The high water treatment capacity was attributed to the much enhanced ZVI reactivity in the magnetic field, sustained through rejuvenation by PUD. Furthermore, most of As was structurally incorporated into the produced iron (oxyhydr)oxides (mostly ferrihydrite) in the MCCR-PUD, as revealed by Mössbauer spectroscopy, X-ray absorption spectroscopy, and sequential extraction experiments. This finding evinced a different mechanism from the surface adsorption in the ZVI/sand filter. The structural incorporation of As also resulted in much less As remobilization from the produced corrosion products during aging in water, in total ∼1 % in 28 days. Furthermore, the MCCR-PUD exihibted robust performance when treating complex synthetic groundwater containing natural organic matter and common ions (∼3700 EBV at breakthrough). Taken together, our study demonstrates the potential of the magnetic confinement-enabled ZVI reactor as a promising decentralized As treatment platform.

Investigating Medin Cleavage Accessibility in MfgE8: Conformational Insights Derived from Molecular Dynamics Simulations and AlphaFold2 Models.

Recent studies have indicated that the human amyloidogenic protein medin is associated with a range of vascular diseases, including aortic aneurysms, vascular dementia, and Alzheimer's disease. Medin accumulates in the vasculature with age, leading to endothelial dysfunction through oxidative and nitrative stress and inducing pro-inflammatory activation. Medin is a cleavage product from the C2 domain of MfgE8. The exact mechanism of medin production from MfgE8 is unknown, with crystal structures of homologous C2 domains suggesting that the cleavage sites are buried, requiring a conformational transition for medin production. Molecular dynamics simulations can explore a wide range of conformations, from small-scale bond rotations to large-scale changes like protein folding or ligand binding. This study employed a combination of full-atom and coarse-grained molecular dynamics simulations, along with CONCOORD- and AlphaFold2-generated models, to investigate MfgE8 conformations and their implications for medin cleavage site accessibility. The simulations revealed that MfgE8 tends to adopt a compact conformation with the RGD motif, important for cell attachment within the N-terminal domain, and the medin region in the C-terminal domain close in proximity. Formation of this compact structure is facilitated by interdomain electrostatic interactions that promote stability and in turn decrease the solvent-accessible surface area of the medin region and particularly the C-terminal medin cleavage site. This data enhances current knowledge on medin generation to propose that alterations in local environmental conditions, possibly through changes in glycosylation or other post-translational modifications are required to induce MfgE8 to unfold partially or fully: this would result in enhanced accessibility of the cleavage sites and therefore enable medin generation.

Global profiling of protein lactylation in microglia in experimental high-altitude cerebral edema

BackgroundHigh-altitude cerebral edema (HACE) is considered an end-stage acute mountain sickness (AMS) that typically occurs in people after rapid ascent to 2500 m or more. While hypoxia is a fundamental feature of the pathophysiological mechanism of HACE, emerging evidence suggests that inflammation serves as a key risk factor in the occurrence and development of this disease. However, little is known about the molecular mechanism underlying their crosstalk.MethodsA mouse HACE model was established by combination treatment with hypobaric hypoxia exposure and lipopolysaccharides (LPS) stimulation. Lactylated-proteomic analysis of microglia was performed to reveal the global profile of protein lactylation. Molecular modeling was applied to evaluate the 3-D modeling structures. A combination of experimental approaches, including western blotting, quantitative real-time reverse transcriptionpolymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA), confocal microscopy and RNA interference, were used to explore the underlying molecular mechanisms.ResultsWe found that hypoxia exposure increased the lactate concentration and lactylation in mouse HACE model. Moreover, hypoxia aggravated the microglial neuroinflammatory response in a lactate-dependent manner. Global profiling of protein lactylation has shown that a large quantity of lysine-lactylated proteins are induced by hypoxia and preferentially occur in protein complexes, such as the NuRD complex, ribosome biogenesis complex, spliceosome complex, and DNA replication complex. The molecular modeling data indicated that lactylation could affect the 3-D theoretical structure and increase the solvent accessible surface area of HDAC1, MTA1 and Gatad2b, the core members of the NuRD complex. Further analysis by knockdown or selectively inhibition indicated that the NuRD complex is involved in hypoxia-mediated aggravation of inflammation.ConclusionsThese results revealed a comprehensive profile of protein lactylation in microglia and suggested that protein lysine lactylation plays an important role in the regulation of protein function and subsequently contributes to the neuroinflammatory response under hypoxic conditions.

Functional characterization and structural prediction of hypothetical proteins in monkeypox virus and identification of potential inhibitors.

The excessive activation of the monkeypox virus (MPXV-Congo_8-156) is linked to various skin and respiratory disorders such as rashes, fluid-filled blisters, swollen lymph nodes and encephalitis (inflammation of the brain), highlighting MPXV-Congo_8-156 as a promising target for drug intervention. Despite the effectiveness of Cidofovir, in inhibiting MPXV activity, its limited ability to penetrate the skin and its strong side effects restrict its application. To address this challenge, we screened 500 compounds capable of penetrating the skin and gastrointestinal tract to identify potent MPXV inhibitors. Various characterization schemes and structural models of MPXV-Congo_8-156 were explored with bioinformatics tools like PROTPARAM, SOPMA, SWISS-MODEL and PROCHECK. Using molecular docking in PyRx, we evaluated the binding affinities of these compounds with MPXV-Congo_8-156 and identified the top five candidates ranging from - 9.2 to - 8.8kcal/mol. ADMET analysis indicated that all five compounds were safer alternatives, showing no AMES toxicity or carcinogenicity in toxicological assessments. Molecular dynamics (MD) simulations, conducted for 100ns each, confirmed the docking interactions of the top five compounds alongside the control (Cidofovir), validating their potential as MPXV inhibitors. The compounds with PubChem CID numbers 4061636, 4422538, 3583576, 4856107 and 4800629 demonstrated strong support in terms of root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA) value, hydrogen bond analysis, and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis. Thus, our investigation identified these five compounds as promising inhibitors of MPXV, offering potential therapeutic avenues. However, further in vivo studies are necessary to validate our findings.

Molecular-Scale Liquid Density Fluctuations and Cavity Thermodynamics.

Equilibrium density fluctuations at the molecular level produce cavities in a liquid and can be analyzed to shed light on the statistics of the number of molecules occupying observation volumes of increasing radius. An information theory approach led to the conclusion that these probabilities should follow a Gaussian distribution. Computer simulations confirmed this prediction across various liquid models if the size of the observation volume is not large. The reversible work required to create a cavity and the chance of finding no molecules in a fixed observation volume are directly correlated. The Gaussian formula for the latter probability is scrutinized to derive the changes in enthalpy and entropy, which arise from the cavity creation. The reversible work of cavity creation has a purely entropic origin as a consequence of the solvent-excluded volume effect produced by the inaccessibility of a region of the configurational space. The consequent structural reorganization leads to a perfect compensation of enthalpy and entropy changes. Such results are coherent with those obtained from Lee in his direct statistical mechanical study.