Strong Interaction Research Articles

Interlayer and interfacial Dzyaloshinskii-Moriya interaction in magnetic trilayers: First-principles calculations

We determine the Dzyaloshinskii-Moriya interaction within and between two magnetic cobalt layers separated by a nonmagnetic spacer through calculations. We investigate different materials for the nonmagnetic layer, focusing on the experimentally realized Co/Ag/Co system. We laterally shift the atoms in the nonmagnetic layer to achieve the symmetry breaking required for the interlayer Dzyaloshinskii-Moriya interaction. We compare the resulting interactions with the Levy-Fert model and observe a good overall agreement between the model and the calculations for the dependence on the atomic positions. Additionally, we derive a formula for the strength of the interlayer isotropic exchange interaction depending on the position of the atoms in the nonmagnetic layer and compare it to the first-principles results. We investigate the limitations of the Levy-Fert model by turning off the spin-orbit coupling separately on the nonmagnetic and magnetic atoms and by studying the effect of band filling. Our work advances the understanding of the microscopic mechanisms of the interlayer Dzyaloshinskii-Moriya interaction and gives insight into possible new material combinations with strong interlayer Dzyaloshinskii-Moriya interaction. Published by the American Physical Society 2024

Selenium alters the gene content but not the taxonomic composition of the soil microbiome

Abstract Background Microbiomes, essential to ecosystem processes, face strong selective forces that can drive rapid evolutionary adaptation. However, our understanding of evolutionary processes within natural systems remains limited. We investigated evolution in response to naturally occurring selenium in soils of different geological parental materials on the Western Slope of Colorado. Our study focused on examining changes in gene frequencies within microbial communities in response to selenium exposure. Results Despite expectations of taxonomic composition shifts and increased gene content changes at high-selenium sites, we found no significant alterations in microbial diversity or community composition. Surprisingly, we observed a significant increase in differentially abundant genes within high-selenium sites. Conclusions These findings are suggestive that selection within microbiomes primarily drives the accumulation of genes among existing microbial taxa, rather than microbial species turnover, in response to strong stressors like selenium. Our study highlights an unusual system that allows us to examine evolution in response to the same stressor annually in a non-model system, contributing to understanding microbiome evolution beyond model systems.

Development of Mg‐Alginate Based Self Disassociative Bio‐Ink for Magnetic Bio‐Patterning of 3D Tumor Models

AbstractAlginate forms a hydrogel via physical cross‐linking with divalent cations. In literature, Ca2+ is mostly utilized due to strong interactions but additional procedures are required to disassociate Ca‐alginate hydrogels. On the other hand, Mg‐alginate hydrogels disassociate spontaneously, which might benefit certain applications. This study introduces Mg‐alginate as the main component of a bio‐ink for the first time to obtain 3D tumor models by magnetic bio‐patterning technique. The bio‐ink contains magnetic nanoparticles (MNPs) for magnetic manipulation, Mg‐alginate hydrogel as a sacrificial material, and cells. The applicability of the methodology is tested for the formation of 3D tumor models using HeLa, SaOS‐2, and SH‐SY5Y cells. Long‐term cultures are examined by Live/dead and MTT analysis and revealed high cell viability. Subsequently, Collagen and F‐actin expressions are observed successfully in 3D tumor models. Finally, the anti‐cancer drug Doxorubicin (DOX) effect is investigated on 3D tumor models, and IC50 values is calculated to assess the drug response. As a result, significantly higher drug resistance is observed for bio‐patterned 3D tumor models up to tenfold compared to 2D control. Overall, Mg‐alginate hydrogel is successfully used to form bio‐patterned 3D tumor models, and the applicability of the model is shown effectively, especially as a drug screening platform.

Abstract B008: Therapy-protective peristromal niches mediate positive ecological interaction between therapy-sensitive and therapy-resistant cells, altering the evolutionary dynamics of acquired targeted therapy resistance in lung cancers

Abstract Pharmacological inhibitors of oncogenic signaling, such as drugs that target ALK kinase (ALKi) in ALK+ lung cancers, can induce strong and durable clinical responses. However, targeted therapies are not curative in advanced cancers and even strong responders eventually develop resistance. While therapy resistance is typically attributed to cell-intrinsic (epi)mutational characteristics of tumor cells, it can also result from interactions of tumor cells with the tumor microenvironment (TME). In contrast to the detailed elucidation of the molecular mediators of therapy resistance, our knowledge of the evolutionary dynamics underlying the resistance emergence, including the impact of TME, remains poorly defined. A key open question in understanding the evolutionary dynamics of therapy resistance is whether relapse results from an expansion of pre-existing therapy-resistant subpopulations or from a bona fide gradual evolutionary process. To elucidate this question, we integrated experimental mouse studies with mathematical modeling, interrogating therapeutic responses of therapy-naïve experimental xenograft ALK+ tumors, spiked-in with differentially labeled resistant cells. We found that ALKi treatment induced a rapid expansion of resistant cells, which drastically reduced the magnitude and duration of remissions. Surprisingly, our in silico analyses pointed to the existence of a strong positive ecological interaction between therapy-resistant and therapy-sensitive competitors. Using a combination of spatial analyses, experimental studies, and mathematical modeling, we found that this interaction was mediated by peristromal niches that protected therapy-sensitive tumor cells. Specifically, by limiting tumor regression, the therapy- induced expansion of resistant cells limited the loss of protective peristromal niches, while the subsequent resumption of tumor growth created new peristromal niches capable of supporting the survival and proliferation of therapy-sensitive cells. While this niche-mediated interaction had only a marginal impact on the transition from remission to relapse, enhanced survival of therapy-sensitive cells potentiated their ability to adapt to ALKi, leading to a higher diversity of resistance phenotypes. In summary, our study has revealed a new type of indirect, niche-mediated ecological interaction between therapy-resistant and therapy-sensitive cells. The rapid expansion of rare pre-existent resistant cells and fast transition to relapse challenge a common assumption of the pre-existence of therapy resistance. Finally, our results highlight the essentiality of TME considerations in understanding the evolutionary dynamic underlying the development of therapy resistance. Citation Format: Mark Robertson-Tessi, Bina Desai, Tatiana Miti, Pragya Kumar, Sagnik Yarlagadda, Rishi Shah, Robert Vander Velde, Daria Miroshnychenko, David Basanta, Alexander Anderson, Andriy Marusyk. Therapy-protective peristromal niches mediate positive ecological interaction between therapy-sensitive and therapy-resistant cells, altering the evolutionary dynamics of acquired targeted therapy resistance in lung cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B008.

Quantum Interpretation for Measurements in Physics

The postulate in the Copenhagen interpretation is for quantum measures that in experiments from a set of operators only a subset of commuting operators can be measured simultaneously, the rest remains undetermined. As example the Stern-Gerlach measure shows for spin a 90 degree change and measures for instance spin up and down of the outcome particles only in the z-direction. The spacial xy-coordinates remain undetermined.Using octonion coordinates [1,2] for the quantum range this view can be applied to all octonion base GF triples which use the three noncommuting Pauli matrices. The coordinates are enumerated by indices 0,1,2,…,7. Entanglements of different GF are possible. Two examples are the spin-lepton cases 123 (for xyz) and 145 (1 for electrical EM charge, 4 for magnetism, 5 for leptonic mass) either in the gyromagnetic relation (EM) or the helicty (neutral leptons).A in the second case the Copenhagen interpretation is extended to a quantum interpretation for measurements of the GF. The systems and energies involved can be different. The neutrino N oscillations show that also the Heisenberg uncertainties HU play a role. Spin is aligned with the space coordinate 1 and the momentum p = mv on 6. The HU means that 1,6 cannot be measured sharp. Hence the leptonic kg measure 5 changes for p along the world line of N stochasticaly, observed as oscillation. The kg GF is 257 and has 6 possible values for leptons. The weights of the three GF coordinates are mostly positive real or complex numbers. There are seven octonion GF 123, 145, 167 (for electromagnetic interaction EMI), 246 (for heat, acoustics), 257, 347 (for rotational energy), 356 (for a nucleon inner dynamics). Beside these are for the strong interaction SI three more GF 126 as rgb-graviton , 345 for its dual Dg and 037 for a newly postulated color charge force cc.The new cc force has a different symmetry than the Pauli quaternions.The six complex cross ratios invariant under the Moebius transformations of the Riemannian sphere are discussed in relation to quantum measures.

Bioinspired "Intermolecular Pocket" in Soft Molecular Crystal of Porous Organic CageExhibiting Reversible Guest Recognition.

Porous Organic Cages (POCs) have gathered a lot of attention in sorts of fields. Previous studies often focused on the functionalization of their intrinsic porosity, while the utilization of the extrinsic porosity has been seldom reported. To date, the rational construction of functionalized extrinsic porosity in POCs is a serious challenge, which still relies on trial and error. Inspired by hydrophobic proteins, in the contribution, a POC (namely NKPOC-DS) is obtained with hydrophobic "intermolecular pocket" as extrinsic porosity constructed through the assembly of disulfide bonds with hydrophobic groups, facilitating strong supramolecular interactions as confirmed by Electrostatic Potential (ESP) maps and single-crystal X-ray diffraction analysis. Notably, NKPOC-DS exhibits a unique C2H6-selective "breathing behaviour" due to the presence of softness in its extrinsic porosity, which does not extend to other gases such as C2H4, CH4, CO2, N2, and H2. Such specific recognition of C2H6 thus provides NKPOC-DS with the ability to preferentially adsorb C2H6 from a C2H6/C2H4 mixture. The innovative approach of biomimicry in the design of functional POCs provides new insights into manipulating the packing of cages, paving the way for potential applications in guest recognition and adsorption separations.

Bioinspired “Intermolecular Pocket” in Soft Molecular Crystal of Porous Organic Cage Exhibiting Reversible Guest Recognition

Porous Organic Cages (POCs) have gathered a lot of attention in sorts of fields. Previous studies often focused on the functionalization of their intrinsic porosity, while the utilization of the extrinsic porosity has been seldom reported. To date, the rational construction of functionalized extrinsic porosity in POCs is a serious challenge, which still relies on trial and error. Inspired by hydrophobic proteins, in the contribution, a POC (namely NKPOC‐DS) is obtained with hydrophobic “intermolecular pocket” as extrinsic porosity constructed through the assembly of disulfide bonds with hydrophobic groups, facilitating strong supramolecular interactions as confirmed by Electrostatic Potential (ESP) maps and single‐crystal X‐ray diffraction analysis. Notably, NKPOC‐DS exhibits a unique C2H6‐selective "breathing behaviour" due to the presence of softness in its extrinsic porosity, which does not extend to other gases such as C2H4, CH4, CO2, N2, and H2. Such specific recognition of C2H6 thus provides NKPOC‐DS with the ability to preferentially adsorb C2H6 from a C2H6/C2H4 mixture. The innovative approach of biomimicry in the design of functional POCs provides new insights into manipulating the packing of cages, paving the way for potential applications in guest recognition and adsorption separations.

Comparison of retinol binding protein 1 with cone specific G-protein as putative effector molecules in cryptochrome signalling.

Vision and magnetoreception in navigating songbirds are strongly connected as recent findings link a light dependent radical-pair mechanism in cryptochrome proteins to signalling pathways in cone photoreceptor cells. A previous yeast-two-hybrid screening approach identified six putative candidate proteins showing binding to cryptochrome type 4a. So far, only the interaction of the cone specific G-protein transducin α-subunit was investigated in more detail. In the present study, we compare the binding features of the G-protein α-subunit with those of another candidate from the yeast-two-hybrid screen, cellular retinol binding protein. Purified recombinant European robin retinol binding protein bound retinol with high affinity, displaying an EC50 of less than 5nM, thereby demonstrating its functional state. We applied surface plasmon resonance and a Förster resonance transfer analysis to test for interactions between retinol binding protein and cryptochrome 4a. In the absence of retinol, we observed no robust binding events, which contrasts the strong interaction we observed between cryptochrome 4a and the G-protein α-subunit. We conclude that retinol binding protein is unlikely to be involved in the primary magnetosensory signalling cascade.

Superparamagnetic Iron Oxide Nanoparticles on ZrO2 as Catalysts for CO2 Hydrogenation to Lower Olefins

Organic synthesis presents significant opportunities for converting the abundant and hazardous carbon dioxide (CO2) in the atmosphere into a more sustainable carbon source. To reduce the carbon footprint, we explored the direct hydrogenation of CO2 to lower (C2‐4=) olefins using various catalysts composed of ZrO2‐supported alkali‐metal‐promoted superparamagnetic iron oxide nanoparticles (SPIONs; Fe3O4). These catalysts are notable for their straightforward preparation; we employed a cost‐effective dry‐mixing method to create a range of alkali metal‐doped SPIONs supported on ZrO2. Results showed that the strong interactions between Fe3O4 and the ZrO2 support enhanced CO2 hydrogenation performance compared to other forms, such as pristine Fe or Fe2O3. Under optimal conditions—using a gas hourly space velocity (GHSV) of 4500 mL/h/gcat and a feed ratio of H2:CO2 = 3:1—this catalyst achieved over 22% CO2 conversion and high selectivity for light (C2‐4=) olefins at 30 bar and 375 ºC, with 30 wt% Fe3O4 loading on ZrO2 and 2 wt% K promoter. We also investigated several variables, including alkali metal concentration, iron content, reaction conditions, and catalyst stability over 96 hours.

Lattice Strain Regulated by Hetero/Homo Atom Interface Merging on NiMo Nanocluster for High-Performance Hydrogen Production.

Lattice strain engineering represents a cutting-edge approach capable of delivering enhanced performance across various applications. The lattice strain can affect the performance of electrochemical catalysts by changing the binding energy between the surface-active sites and intermediates. In this work, lattice strain is regulated through a homo/heterogeneous atomic interface merging. The strong lattice strain and electronic interactions between Ni and Mo facilitated the reaction kinetic of HER. The prepared NiMo@SSM exhibits excellent HER catalytic performance with 70 mV overpotential at the current density of 10 mA cm-2 and long-term stability. The method of controlling lattice strain through hetero/homo atom interface merging provides a new strategy for designing high-performance alkaline HER electrocatalysts.

A mechanical qubit.

Although strong nonlinear interactions between quantized excitations are an important resource for quantum technologies based on bosonic oscillator modes, most electromagnetic and mechanical nonlinearities are far too weak to allow for nonlinear effects to be observed at the single-quantum level. This limitation has been overcome in electromagnetic resonators by coupling them to other strongly nonlinear quantum systems such as atoms and superconducting qubits. We demonstrate the realization of the single-phonon nonlinear regime in a solid-state mechanical system. The single-phonon anharmonicity in our system exceeds the decoherence rate by a factor of 6.8, allowing us to use it as a mechanical qubit and demonstrate initialization, readout, and single-qubit gates. Our approach provides a powerful quantum acoustics platform for quantum simulations, sensing, and information processing.

Integrated virtual screening and MD simulation study to discover potential inhibitors of mycobacterial electron transfer flavoprotein oxidoreductase.

Tuberculosis (TB) continues to be a major global health burden, with high incidence and mortality rates, compounded by the emergence and spread of drug-resistant strains. The limitations of current TB medications and the urgent need for new drugs targeting drug-resistant strains, particularly multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, underscore the pressing demand for innovative anti-TB drugs that can shorten treatment duration. This has led to a focus on targeting energy metabolism of Mycobacterium tuberculosis (Mtb) as a promising approach for drug discovery. This study focused on repurposing drugs against the crucial mycobacterial protein, electron transfer flavoprotein oxidoreductase (EtfD), integral to utilizing fatty acids and cholesterol as a carbon source during infection. The research adopted an integrative approach, starting with virtual screening of approved drugs from the ZINC20 database against EtfD, followed by molecular docking, and concluding with molecular dynamics (MD) simulations. Diacerein, levonadifloxacin, and gatifloxacin were identified as promising candidates for repurposing against TB based on their strong binding affinity, stability, and interactions with EtfD. ADMET analysis and anti-TB sensitivity predictions assessed their pharmacokinetic and therapeutic potential. Diacerein and levonadifloxacin, previously unexplored in anti-tuberculous therapy, along with gatifloxacin, known for its efficacy in drug-resistant TB, have broad-spectrum antimicrobial properties and favorable pharmacokinetic profiles, suggesting potential as alternatives to current TB treatments, especially against resistant strains. This study underscores the efficacy of computational drug repurposing, highlighting bacterial energy metabolism and lipid catabolism as fruitful targets. Further research is necessary to validate the clinical suitability and efficacy of diacerein, levonadifloxacin, and gatifloxacin, potentially enhancing the arsenal against global TB.

Force-Assisted Orbital Crossing in Mechanochemical Oxirane Ring Opening.

Polymer mechanochemistry induces chemical reactivity by applying a directed force, which can lead to unexpected reaction mechanisms. Strained cyclic molecules are often used in force-sensitive motifs because of the strong force coupling of ring-opening reactions. In this computational study, the force dependence of the ring-opening reactions of oxirane will be investigated. Density functional theory and multireference methods were used to investigate the electronic character of both symmetry-allowed and symmetry-forbidden reactions. In the latter case, an orbital crossing occurs during the reaction course, forcing the Woodward-Hoffmann-forbidden reaction to proceed via a diradical pathway. The performance of broken-symmetry density functional theory is evaluated and compares well to high-accuracy CASPT2, MRCI, and ic-MRCC computations. Due to the high ring strain, the barrier heights of both ring-opening reactions are steeply reduced by the application of an external force. Furthermore, the use of unsaturated linkers was shown to yield a significant reduction of the barrier heights, explaining previous experimental findings. Finally, we show through analysis of the PES topology how the external force transforms characteristic points such as saddle points and bifurcations, providing insights into force-dependent mechanism changes.

Cocrystallization Enables Ensitrelvir to Overcome Anomalous Low Solubility Caused by Strong Intermolecular Interactions between Triazine-Triazole Groups in Stable Crystal Form.

Ensitrelvir is a nonpeptide 3CL protease inhibitor used for coronavirus disease 2019 treatment. Four crystalline forms of ensitrelvir, metastable (Form I), acetonate (Form II), stable (Form III), and hydrate (Form IV), have been analyzed as pharmaceutical crystals. Their rank order of solubility is Form I > IV > III. Form III is the stable crystal with a significantly lower solubility than that predicted from its log P value of 2.7. Here, single-crystal structural analysis revealed strong intermolecular interactions between the triazine (acidic) and triazole (basic) groups of Form III not Forms I and IV. Multicomponent crystals were also designed to improve the solubility by altering the intermolecular interactions in Form III. Slurry conversion with equal molar ratios of ensitrelvir and fumaric acid successfully induced the formation of a novel cocrystal (Form V). Fumaric acid inhibited the triazine-triazole interactions, and dissolution of Form V was approximately 8- and 13-fold higher than that of Form III in pH 1.2 and 6.8 media, respectively. Furthermore, Form V exhibited an approximately 16-fold higher flux value than that of Form III. Therefore, alterations in intermolecular interactions via cocrystallization significantly enhance the dissolution and permeation of ensitrelvir.

Environmental Cationic Dye/Porous Silica Nanospheres for Printed Cotton Fabrics with Enhanced Coloration Performance.

The wastewater of printing and dyeing is difficult to treat due to the degradation resistance of dye and the use of massive chemicals, causing a threat to the ecosystem. Pigment printing of fabrics possesses great advantages like high efficiency and flexible production, but there are some challenges like the risk of color depth and hand feeling due to the large size of the pigment and poor adsorption of light. In order to improve the coloration ability of pigment, herein, a novel kind of cationic dye/porous silica nanospheres were prepared through the adsorption of methylene blue and rhodamine B onto electronegative porous silica nanospheres and applied in printing on woven cotton fabric. It was found that the nanospheres exhibited an average diameter, good color depth, hand feeling, and high image quality for pigment preparation. In comparison with dye-printed fabrics, fabrics with dye/WHMS show higher color depth, resulting from the lower visible light reflectance. Notably, the strong interaction between dyes and hydrophilic porous silica nanospheres (WHMS) facilitates the improvement of absorption efficiency and stability. Meanwhile, the printed fabrics with dye/WHMS demonstrate splendid color fastness. The dry/wet rubbing fastnesses are 4 and 3-4, respectively. Furthermore, dye/WHMS-printed cotton fabrics possess a satisfactory hand feeling and breathability. The consumptions of dye wastewater were reduced, and the printing process was simplified. We think that this work may provide a novel insight into printed textiles with enhanced color effects and alleviate the environmental impact of conventional textile coloration.

Radiation-induced nanogel engineering based on pectin for pH-responsive rutin delivery for cancer treatment.

This research investigates the formulation of a nanogel complex using pectin and poly(acrylic acid) (PAAc) to encapsulate rutin. The nanogel's pH-responsive behavior and its potential as a targeted drug delivery platform are investigated. The gamma irradiation-induced crosslinking mechanism is elucidated, highlighting its role in creating a stable three-dimensional network structure within the polymer matrix. Fourier transform infrared spectroscopy analysis sheds light on the molecular interactions within rutin and the nanogel-rutin complex. The pH-responsive behavior of the nanogel is explored, showcasing its ability to release rutin selectively in response to pH variations and displaying high physical and chemical stability. Transmission electron microscopy imaging provides visual insights into nanogel morphology and interactions. The cumulative drug content from the nanogel was 86.14 ± 2.61%. The pH-dependent release profile of the nanogel was examined, demonstrating selective rutin release in response to varying pH levels. Cytotoxicity studies were conducted against four human cancer cell lines-HepG2, A549, MCF-7, and HCT-116 showing significant reductions in IC50 values, indicating enhanced therapeutic efficacy. Additionally, molecular docking studies revealed strong binding interactions of rutin with VEGFR-2 and EGFRT790M. Our nanogel compound 5 significantly reduced the IC50 values for HepG2, A549, MCF-7, and HCT-116 cells by 58.19%, 81.29%, 71.81%, and 67.16%, respectively. Furthermore, it lowered the IC50 values for VEGFR-2 and EGFRT790M by 29.66% and 68.18%, respectively.

Increased Formation of Trions and Charged Biexcitons by Above-Gap Excitation in Single-layer WSe2.

Two-dimensional semiconductors exhibit pronounced many-body effects and intense optical responses due to strong Coulombic interactions. Consequently, subtle differences in photoexcitation conditions can strongly influence how the material dissipates energy during thermalization. Here, using multiple excitation spectroscopies, we show that a distinct thermalization pathway emerges at elevated excitation energies, enhancing the formation of trions and charged biexcitons in single-layer WSe2 by up to 2× and 5× , respectively. Power- and temperature-dependent measurements lend insights into the origin of the enhancement. These observations underscore the complexity of excited state relaxation in monolayer semiconductors, provide insights for the continued development of carrier thermalization models, and highlight the potential to precisely control excitonic yields and probe nonequilibrium dynamics in 2D semiconductors.

Proteomic profiling of oral squamous cell carcinoma tissues reveals altered immune-related proteins: implications for personalized therapy

ABSTRACT Objectives Oral squamous cell carcinoma poses a substantial global health challenge marked by rising mortality rate. Recently, immunotherapy has shown promising results in cancer management by enhancing immune response. Thus, identifying additional immune-related markers is critical for advancing immunotherapy treatments. Methods Data-independent acquisition (DIA) mass spectrometry approach was used to explore differentially expressed immune-related proteins in oral cancer tissues compared to adjacent non-cancerous tissues. Functional significance was identified through Gene Ontology, pathway, and network analysis. Gene expression of identified proteins was validated using transcriptomic data. Results DIA analysis identified 29,459 precursors corresponding to 3429 proteins. Among these, 1060 proteins were differentially expressed, with 166 being immune-related. Differentially regulated proteins were involved in innate immune response, mitochondrial ATP synthesis, and neutrophil degranulation. Pathway analysis of immune-related proteins showed perturbation in anti-tumor immunity-related pathways such as interferon signaling, TCR signaling, PD-1 signaling, and antigen processing and presentation. Significance of these pathways was further reinforced by the strong interactions identified in the protein–protein interaction network analysis. Additionally, gene expression analysis showed similar mRNA expression patterns for key proteins involved in altered pathways, including ISG15, IFIT1/3, HLA-A/C and OAS2/3. Conclusions Further validation of these proteins could establish them as potential targets for personalized therapy.

Myc 9aaTAD activation domain binds to mediator of transcription with superior high affinity.

The overexpression of MYC genes is frequently found in many human cancers, including adult and pediatric malignant brain tumors. Targeting MYC genes continues to be challenging due to their undruggable nature. Using our prediction algorithm, the nine-amino-acid activation domain (9aaTAD) has been identified in all four Yamanaka factors, including c-Myc. The predicted activation function was experimentally demonstrated for all these short peptides in transactivation assay. We generated a set of c-Myc constructs (1-108, 69-108 and 98-108) in the N-terminal regions and tested their ability to initiate transcription in one hybrid assay. The presence and absence of 9aaTAD (region 100-108) in the constructs strongly correlated with their activation functions (5-, 3- and 67-times respectively). Surprisingly, we observed co-activation function of the myc region 69-103, called here acetyl-TAD, previously described by Faiola et al. (Mol Cell Biol 25:10220-10234, 2005) and characterized in this study as a new domain collaborating with the 9aaTAD. We discovered strong interactions on a nanomolar scale between the Myc-9aaTAD activation domains and the KIX domain of CBP coactivator. We showed conservation of the 9aaTADs in the MYC family. In summary for the c-Myc oncogene, the acetyl-TAD and the 9aaTAD domains jointly mediated activation function. The c-Myc protein is largely intrinsically disordered and therefore difficult to target with small-molecule inhibitors. For the c-Myc driven tumors, the strong c-Myc interaction with the KIX domain represents a promising druggable target.

Controlling Metal-Support Interactions to Engineer Highly Active and Stable Catalysts for COx Hydrogenation.

This perspective focuses on the modulation of metal-support interaction (MSI) in catalysts for COx hydrogenation, highlighting their profound impact on catalytic performance. Firstly, it outlines different strategies, including the use of highly reducible oxides and moderate reduction treatments, which induce the classical strong metal-support interaction (SMSI) effect and the electronic metal-support interaction (EMSI) effect. Morphology engineering and crystalline phase manipulation of oxides presented as effective methods to control EMSI are also discussed. The discrimination of SMSI and EMSI can be achieved using oxides with low encapsulation tendencies, such as ZrO2, which supports electronic modifications without or minimizing the overgrowth issues, optimizing the catalytic performance for methanation. Then, the synergy between Cu and ZnO in methanol synthesis, enhanced by SMSI, is emphasized inside. Optimizing support oxides to control oxygen vacancies enhances the catalytic performance of CO2 hydrogenation to methanol. Perspectives for the future research on the fundamental understanding of structure-MSI-performance relationship for catalyst design is discussed.