Modulation Of Interactions Research Articles

Water-Stable Zero-Dimensional Hybrid Zinc Halide Modulated by π-π Interactions: Efficient Blue Light Emission and Third-Order Nonlinear Optical Response

Achieving multifunctional optimization of halide optical materials through the precise modulation of intermolecular interactions is highly significant, yet it faces considerable challenges. Here, we propose a strategy of π-π interactions...

Modulation of intermolecular interactions in hole transporting materials for improvement of perovskite solar cell efficiency: a strategy of trifluoromethoxy isomerization

A trifluoromethoxy isomerization strategy to modulate intermolecular interactions is proposed to balance the intermolecular interactions of hole transport materials and their interface interactions with perovskites.

Cholesterol modulation of interactions between psychostimulants and dopamine transporters.

The dopamine transporter (DAT) is a key site of action for cocaine and amphetamines. Dysfunctional DAT is associated with aberrant synaptic dopamine transmission and enhanced drug-seeking and taking behavior. Studies in cultured cells and ex vivo suggest that DAT function is sensitive to membrane cholesterol content. Although it is largely unknown whether psychostimulants alter cholesterol metabolism in the brain, emerging evidence indicates that peripheral cholesterol metabolism is altered in patients with psychostimulant use disorder and circulating cholesterol levels are associated with vulnerability to relapse. Cholesterol interacts with sphingolipids forming lipid raft microdomains on the membrane. These cholesterol-rich lipid raft microdomains serve to recruit and assemble other lipids and proteins to initiate signal transduction. There are two spatially and functionally distinct populations of the DAT segregated by cholesterol-rich lipid raft microdomains and cholesterol-scarce non-raft microdomains on the plasma membrane. These two DAT populations are differentially regulated by DAT blockers (e.g. cocaine), substrates (e.g. amphetamine), and protein kinase C providing distinct cholesterol-dependent modulation of dopamine uptake and efflux. In this chapter, we summarize the impact of depletion and addition of membrane cholesterol on DAT conformational changes between the outward-facing and the inward-facing states, lipid raft-associated DAT localization, basal and induced DAT internalization, and DAT function. In particular, we focus on how the interactions of the DAT with cocaine and amphetamine are influenced by membrane cholesterol. Lastly, we discuss the therapeutic potential of cholesterol-modifying drugs as a new avenue to normalize DAT function and dopamine transmission in patients with psychostimulant use disorder.

A bioinspired approach for the modulation of electroosmotic flow and protein-surface interactions in capillary electrophoresis using silylated amino-amides blocks and covalent grafting.

We explore a bioinspired approach to design tailored functionalized capillary electrophoresis (CE) surfaces based on covalent grafting for biomolecules analysis. First, the approach aims to overcome well-known common obstacles in CE protein analysis affecting considerably the CE performance (asymmetry, resolution, and repeatability) such as the unspecific adsorption on fused silica surface and the lack of control of electroosmotic flow (EOF). Then, our approach, which relies on new amino-amide mimic hybrid precursors synthesized by silylation of amino-amides (Si-AA) derivatives with 3-isocyanatopropyltriethoxysilane, aims to recapitulate the diversity of protein-protein interactions (π-π stacking, ionic, Van der Waals…) found in physiological condition (bioinspired approach) to improve the performance of CE protein analysis (electrochromatography). As a proof of concept, these silylated Si-AA (tyrosinamide silylation, serinamide silylation, argininamide silylation, leucinamide silylation, and isoglutamine silylation acid) have been covalently grafted in physiological conditions in different amount on bare fused silica capillary giving rise to a biomimetic coating and allowing both the modulation of EOF and protein-surface interactions. The analytical performances of amino-amide functionalized capillaries were assessed using lysozyme, cytochrome C and ribonuclease A and compared to traditional capillary coatings poly(ethylene oxide), poly(diallyldimethylammonium chloride), and sodium poly(styrenesulfonate). EOF, protein adsorption rate, protein retention factor k, and selectivity were determined for each coating. All results obtained showed this approach allowed to modulate the EOF, reduce unspecific adsorption, and generate specific interactions with proteins by varying the nature and the amount of Si-AA in the functionalization mixture.

Organic Donor-Acceptor Systems for Photocatalysis.

Organic semiconductor materials are considered to be promising photocatalysts due to their excellent light absorption by chromophores, easy molecular structure tuning, and solution-processable properties. In particular, donor-acceptor (D-A) type organic photocatalytic materials synthesized by introducing D and A units intra- or intermolecularly, have made great progress in photocatalytic studies. More and more studies have demonstrated that the D-A type organic photocatalytic materials combine effective carrier separation, tunable bandgap, and sensitive optoelectronic response, and are considered to be an effective strategy for enhancing light absorption, improving exciton dissociation, and optimizing carrier transport. This review provides a thorough overview of D-A strategies aimed at optimizing the photocatalytic performance of organic semiconductors. Initially, essential methods for modifying organic photocatalytic materials, such as interface engineering, crystal engineering, and interaction modulation, are briefly discussed. Subsequently, the review delves into various organic photocatalytic materials based on intramolecular and intermolecular D-A interactions, encompassing small molecules, conjugated polymers, crystalline polymers, supramolecules, and organic heterojunctions. Meanwhile, the energy band structures, exciton dynamics, and redox-active sites of D-A type organic photocatalytic materials under different bonding modes are discussed. Finally, the review highlights the advanced applications of organic photocatalystsand outlines prospective challenges and opportunities.

Robust Retrieval of Dynamic Sequences through Interaction Modulation

Robust Retrieval of Dynamic Sequences through Interaction Modulation

Regulating Electron Metal-Support Interaction to Suppress N2O Formation in the Selective Catalytic Oxidation of Ammonia.

N2O is a common byproduct in the selective catalytic oxidation of ammonia, and its generation often needs to be inhibited due to its strong greenhouse effect. In this paper, using Ag/ZSO-Y as a model catalyst, the N2O selectivity was reduced by 30% through modulation of the electron metal-support interaction. The results demonstrate that the work function of the support can be regulated by the content of the doping element. As the Zr content increases in SnO2, the work function of the support decreases. Moreover, there is a positive correlation between the charge transfer amount and the work function of the support. A series of in situ DRIFTS and density functional theory calculations revealed that the -NO and -N reactions are the primary pathways for N2O formation. By adjustment of the work function of the support through varying the Zr doping level, the electronic structure of Ag NPs was further tuned, resulting in an increased reaction energy barrier for -NO and -N reactions, effectively suppressing N2O formation.

Central neuropathic pain.

Central neuropathic pain arises from a lesion or disease of the central somatosensory nervous system such as brain injury, spinal cord injury, stroke, multiple sclerosis or related neuroinflammatory conditions. The incidence of central neuropathic pain differs based on its underlying cause. Individuals with spinal cord injury are at the highest risk; however, central post-stroke pain is the most prevalent form of central neuropathic pain worldwide. The mechanisms that underlie central neuropathic pain are not fully understood, but the pathophysiology likely involves intricate interactions and maladaptive plasticity within spinal circuits and brain circuits associated with nociception and antinociception coupled with neuronal hyperexcitability. Modulation of neuronal activity, neuron-glia and neuro-immune interactions and targeting pain-related alterations in brain connectivity, represent potential therapeutic approaches. Current evidence-based pharmacological treatments include antidepressants and gabapentinoids as first-line options. Non-pharmacological pain management options include self-management strategies, exercise and neuromodulation. A comprehensive pain history and clinical examination form the foundation of central neuropathic pain classification, identification of potential risk factors and stratification of patients for clinical trials. Advanced neurophysiological and neuroimaging techniques hold promise to improve the understanding of mechanisms that underlie central neuropathic pain and as predictive biomarkers of treatment outcome.

Abstract C037: Bile acid modulation of immune cell interactions in the colonic microenvironment

Abstract Colorectal cancer (CRC) is the third most frequent cancer in both women and men, particularly among African Americans (AA). Factors such as ethnicity group, gut microbiota, and Western diet play a significant role in CRC development. However, the impact of ethnicity on the immunological mechanisms involved in CRC is poorly understood. In our study, we collected stool and serum samples from high-risk and low-risk AA and NHW subjects to analyze the fecal bile acid metabolome. We found that certain bile acid isoforms, particularly in allo-bile acids, were significantly reduced in the stool compared to Non-Hispanic White (NHW) females. Clinical mucosal RNA data we generated via the NanoString nCounter platform, revealed in both AA and NHW low-risk female groups, the expression of FoxP3, correlated with immune checkpoints including PDCD1, IDO1, CTLA4 and LAG3 were lowered. Recent findings suggest that allo-bile acids influence the balance between pro-inflammatory TH17 cells and anti-inflammatory Tregs through specific signaling pathways. Based on our data and existing literature, we propose that bacterial-derived allo-bile acids modulate interactions between other myeloid-lineage immune cells, thereby affecting the inflammatory environment of the colon and potentially influencing CRC development. Citation Format: Hanchu Dai, Patricia Wolf, Ece Mutlu, Lisa Tussing-Humphreys, Jason Ridlon, Rex Gaskins. Bile acid modulation of immune cell interactions in the colonic microenvironment [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C037.

Mussel-Inspired Cation-π Interactions: Wet Adhesion and Biomimetic Materials.

Cation-π interaction is one of the most important noncovalent interactions identified in biosystems, which has been proven to play an essential role in the strong adhesion of marine mussels. In addition to the well-known catecholic amino acid, l-3,4-dihydroxyphenylalanine, mussel foot proteins are rich in various aromatic moieties (e.g., tyrosine, phenylalanine, and tryptophan) and cationic residues (e.g., lysine, arginine, and histidine), which favor a series of short-range cation-π interactions with adjustable strengths, serving as a prototype for the development of high-performance underwater adhesives. This work highlights our recent advances in understanding and utilizing cation-π interactions in underwater adhesives, focusing on three aspects: (1) the investigation of the cation-π interaction mechanisms in mussel foot proteins via force-measuring techniques; (2) the modulation of cation-π interactions in mussel mimetic polymers with the variation of cations, anions, and aromatic groups; (3) the design of wet adhesives based on these revealed principles, leading to functional materials in the form of films, coacervates, and hydrogels with biomedical and engineering applications. This review provides valuable insights into the development and optimization of smart materials based on cation-π interactions.

Local and cooperative structural transitions of double-stranded DNA in choline-based deep eutectic solvents

The possibility of using deep eutectic solvents (DESs) as co-solvents for stabilizing and preserving the native structure of DNA provides an attractive opportunity in the field of DNA biotechnology. The rationale of this work is a systematic investigation of the effect of hydrated choline-based DES on the structural stability of a 30-base-pair double-stranded DNA model via a combination of spectroscopic experiments and MD simulations. UV absorption and CD experiments provide evidence of a significant contribution of DESs to the stabilization of the double-stranded canonical (B-form) DNA structure. Multi-wavelength synchrotron UV Resonance Raman (UVRR) measurements indicate that the hydration shell of adenine-thymine pairs is strongly perturbed in the presence of DESs and that the preferential interaction between H-bond sites of guanine residues and DESs is significantly involved in the stabilization of the dsDNA. Finally, MD calculations show that the minor groove of DNA is significantly selective for the choline part of the investigated DESs compared to the major groove. This finding is likely to have a significant impact not only in terms of thermal stability but also in the modulation of ligand-DNA interactions.

Effect of temperature on organic fouling and cleaning efficiency of nanofiltration membranes for loch water treatment

We investigated the effect of solution temperature on organic fouling and cleaning of polypiperazine nanofiltration (NF) membranes. Fouling experiments were conducted in the temperature range 5 °C ≤ T ≤ 15 °C, characteristic of surface waters in northern latitudes, such as Scottish lochs. Results of laboratory-scale fouling experiments using alginate, a polysaccharide constituent of extracellular polymeric substances, showed a moderate increase in flux loss at 15 °C (41 %) compared to 5 °C (36 %). Analysis of the fouling experiments using a series-resistance model showed that the greater extent of fouling with rising temperature stems from a monotonic increase in water permeance with T. Interfacial property characterisation provided further insight into the effect of temperature on fouling determinants such as membrane hydrophobicity, nanoscale roughness, surface charge, and surface forces. No T-dependence of surface roughness was found. Similarly, we found that water contact angle is invariant within the temperature range investigated, suggesting that the observed fouling behaviour is not due to modulation of hydrophobic interactions. Conversely, colloidal-probe force spectroscopy (CPFS) measurements showed that adhesion forces become stronger with rising temperature. Further analysis showed that repulsive forces – which oppose colloidal particle deposition – become weaker with rising temperature, consistent with fouling trends. Determination of the membrane zeta potential showed that surface charge is invariant over the range of temperatures investigated, suggesting that repulsive forces have a non-electrostatic (likely steric) origin. Additionally, we assessed the effect of temperature on physical and chemical cleaning efficiency, comparing cleaning at the same temperature as the fouling experiments (5 °C ≤ T ≤ 15 °C) with cleaning at 30 °C. We observed that physical cleaning, consisting of water circulation over the fouled membrane surface, is insufficient to remove the foulant layers. On the other hand, chemical cleaning is able to restore 95 % of the original membrane permeance at 10 °C, but only 74 % at 5 °C.

Biodegradable Cardiac Occluder with Surface Modification by Gelatin-Peptide Conjugate to Promote Endogenous Tissue Regeneration.

Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long-term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone/poly (l-lactic acid)-gelatin-A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein-derived peptides (A5G81) to the surface of polydioxanone and poly (l-lactic acid) fibers. The polymer microfiber-biomacromolecule-peptide frame with biophysical and biochemical cues could orchestrate the biomaterial-host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti-inflammatory phenotypes and augmenting the release of reparative cytokines. In a porcine atrial septal defect (ASD) model, PGAG occluders promote in situ tissue regeneration by accelerating surface endothelialization and regulating immune response, which mitigate inflammation and fibrosis formation, and facilitate the fusion of occluder with surrounding heart tissue. Collectively, this work highlights the modulation of cell-biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell-material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices.

Discovery of 14-3-3 PPI Stabilizers by Extension of an Amidine-Substituted Thiophene Fragment.

Protein-protein interaction (PPI) modulation is a promising approach in drug discovery with the potential to expand the 'druggable' proteome and develop new therapeutic strategies. While there have been significant advancements in methodologies for developing PPI inhibitors, there is a relative scarcity of literature describing the 'bottom-up' development of PPI stabilizers (Molecular Glues). The hub protein 14-3-3 and its interactome provide an excellent platform for exploring conceptual approaches to PPI modulation, including evolution of chemical matter for Molecular Glues. In this study, we employed a fragment extension strategy to discover stabilizers for the complex of 14-3-3 protein and an Estrogen Receptor alpha-derived peptide (ERα). A focused library of analogues derived from an amidine-substituted thiophene fragment enhanced the affinity of the 14-3-3/ERα complex up to 6.2-fold. Structure-activity relationship (SAR) analysis underscored the importance of the newly added, aromatic side chain with a certain degree of rigidity. X-ray structural analysis revealed a unique intermolecular π-π stacking binding mode of the most active analogues, resulting in the simultaneous binding of two molecules to the PPI binding pocket. Notably, analogue 11 displayed selective stabilization of the 14-3-3/ERα complex.

Theoretical Examination of the Hydroxide Transport in Cobaltocenium-Containing Polyelectrolytes.

Polymers incorporating cobaltocenium groups have received attention as promising components of anion-exchange membranes (AEMs), exhibiting a good balance of chemical stability and high ionic conductivity. In this work, we analyze the hydroxide diffusion in the presence of cobaltocenium cations in an aqueous environment based on the molecular dynamics of model systems confined in one dimension to mimic the AEM channels. In order to describe the proton hopping mechanism, the forces are obtained from the electronic structure computed at the density-functional tight-binding level. We find that the hydroxide diffusion depends on the channel size, modulation of the electrostatic interactions by the solvation shell, and its rearrangement ability. Hydroxide diffusion proceeds via both the vehicular and structural diffusion mechanisms with the latter playing a larger role at low diffusion coefficients. The highest diffusion coefficient is observed under moderate water densities (around half the density of liquid water) when there are enough water molecules to form the solvation shell, reducing the electrostatic interaction between ions, yet there is enough space for the water rearrangements during the proton hopping. The effects of cobaltocenium separation, orientation, chemical modifications, and the role of nuclear quantum effects are also discussed.

Understanding the Role of Activation Loop Mutants in Drug Efficacy for FLT3-ITD.

The type III receptor tyrosine kinase FLT3 is a pivotal kinase for hematopoietic progenitor cell regulation, with significant implications in acute myeloid leukemia (AML) through mutations like internal tandem duplication (ITD). This study delves into the structural intricacies of FLT3, the roles of activation loop mutants, and their interaction with tyrosine kinase inhibitors. Coupled with this, the research leverages molecular contrastive learning and protein language modeling to examine interactions between small molecule inhibitors and FLT3 activation loop mutants. Utilizing the ConPLex platform, over 5.7 million unique FLT3 activation loop mutants-small molecule pairs were analyzed. The binding free energies of three inhibitors were assessed, and cellular apoptotic responses were evaluated under drug treatments. Notably, the introduction of the Xepto50 scoring system provides a nuanced metric for drug efficacy. The findings underscore the modulation of molecular interactions and cellular responses by Y842 mutations in FLT3-KD, highlighting the need for tailored therapeutic approaches in FLT3-ITD-related malignancies.

Modulation of protein-saccharide interactions by deep-sea osmolytes under high pressure stress

Deep-sea organisms must cope with high hydrostatic pressures (HHP) up to the kbar regime to control their biomolecular processes. To alleviate the adverse effects of HHP on protein stability most organisms use high amounts of osmolytes. Little is known about the effects of these high concentrations on ligand binding. We studied the effect of the deep-sea osmolytes trimethylamine-N-oxide, glycine, and glycine betaine on the binding between lysozyme and the tri-saccharide NAG3, employing experimental and theoretical tools to reveal the combined effect of osmolytes and HHP on the conformational dynamics, hydration changes, and thermodynamics of the binding process. Due to their different chemical makeup, these cosolutes modulate the protein-sugar interaction in different ways, leading to significant changes in the binding constant and its pressure dependence. These findings suggest that deep-sea organisms may down- and up-regulate reactions in response to HHP stress by altering the concentration and type of the intracellular osmolyte.

Analysis of single-cell RNA sequencing data revealed the upregulation of Wnt signaling pathway and potential biomarkers in Oral Squamous Cell Carcinoma cancer-associated fibroblasts

CAFs (cancer-associated fibroblasts) and tumor-associated p-EMT (partial epithelial mesenchymal transition) cells coexist and contribute to the formation of epithelial tumors like OSCC (oral squamous cell carcinoma). In oral cancer, Wnt signaling pathway contributes to the tumor progression, invasion and metastasis. Here we deeply analyzed Wnt signaling pathway using our previous single-cell RNA-seq data of CAFs and p-EMT tumor cells in OSCC by computational methods. Integrated single-cell RNA sequencing data of OSCC CAF and p-EMT clusters were obtained from our previous study. These cells were from samples being primary tumor, oral cavity location, metastasis information and then analyzed by R, Python to investigate the gene expression, cell-cell communication, gen set enrichment analysis (GSEA) and overall survival analysis across metastasis conditions regarding Wnt signaling pathway. Genes related to Wnt signaling pathway upregulated in CAFs and p-EMT cancer cells, especially under metastasis condition including WNT2, WNT5A, FZD1-4, ROR2 in CAFs, and WNT7B, FZD2/5/6 in p-EMT cells. Cell-cell interaction analysis and GSEA in CAFs and p-EMT tumor cells highlighted non-canonical Wnt signaling pathway in CAFs and canonical Wnt signaling pathway in p-EMT tumor cells. CTHRC1 and SFRP2 were suggested as biomarkers in Wnt signaling pathway of CAFs from the gene expression, GSEA and overall survival analysis. Our study found CTHRC1 and SFRP2 as biomarkers for HSCC and OSCC prognosis belong to CAFs of TME. It might pave the way for targetable treatment based on WNT ligand-receptor interaction and Wnt signaling modulation in OSCC CAFs based on metastatic status.

Untargeted metabolomic profiling in children identifies novel pathways in asthma and atopy

BackgroundAsthma and other atopic disorders can present with varying clinical phenotypes marked by differential metabolomic manifestations and enriched biological pathways. ObjectiveTo identify these unique metabolomic profiles in atopy and asthma. MethodsWe analyzed baseline non-fasted plasma samples from a large multi-site pediatric population of 470 children < 13 years from three different sites in the US and France. Atopy (At+) was defined as skin prick test ≥ 3 mm and/or specific IgE ≥ 0.35 kUi/L, and/or total IgE ≥ 173 IU/mL. Asthma (As+) was based on physician’s diagnosis. The cohort was divided into four groups of varying combinations of As and At and six pairwise analyses were conducted to best assess differential metabolomic profiles between groups. Results210 children were classified as At-As-, 42 as At+As-, 74 as At-As+ and 144 as At+As+. Untargeted global metabolomic profiles were generated through Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy. We applied two independent machine learning classifiers and shortlisted 362 metabolites as discriminant features. Our analysis showed the most diverse metabolomic profile in the At+As+ / At-As- comparison, followed by the At-As+ / At-As- comparison, indicating that asthma is the most discriminant condition associated with metabolomic changes. At+As+ metabolomic profiles were characterized by higher levels of bile acids, sphingolipids, and phospholipids, and lower levels of polyamine, tryptophan, and gamma-glutamyl amino-acids. ConclusionAt+As+ phenotype displays a distinct metabolomic profile suggesting underlying mechanisms such as modulation of host-pathogen and gut microbiota interactions, epigenetic changes in T-cell differentiation, and lower antioxidant properties of the airway epithelium.

A novel proton exchange membrane with long-range ordered proton transport pathways through modulation of interfacial interactions via amino-functionalized polyhedral oligomeric silsesquioxane-grafted graphene oxide

Nano octa-aminopropyl polyhedral oligomeric silsesquioxane (OA-POSS) was grafted into graphene oxide (GO) via covalent bonding to synthesize OA-POSS-g-GO. A novel SP/OA-POSS-g-GO proton exchange membrane was prepared by adding sulfonated poly (ether ether ketone) (SPEEK, SP). OA-POSS was well dispersed on GO to form an ordered acid-base pair with SPEEK, which facilitated the construction of continuous ion channels. GO as a carrier facilitated the construction of long-range proton conduction pathways in the membrane. The strong interactions between OA-POSS and SPEEK along with the synergistic effect of GO modulate the size of ionic clusters and increased the bound water ratio within the membrane. The conductivity of the SP/OA-POSS-g-GO-2 membrane (80 °C, 95% RH) reached 0.2096 S⋅cm−1, which was 1.7 times higher than that of the SPEEK membrane (0.1265 S⋅cm−1). The conductivity of the SP/OA-POSS-g-GO-2 membrane increased at 100 °C and 40% RH, while that of the SPEEK membrane decreased with the temperature increased above 80 °C. The maximum power density of the single cell assembled from the composite membrane reached 305.8 mW⋅cm−2 at 80 °C and 95% RH, which was 1.4 and 1.3 times higher than that of the SPEEK and Nafion 117 membrane, respectively.