Interaction Mechanism Research Articles

Microextraction of steroidal hormones from urine samples using natural deep eutectic solvents: insights into chemical interactions using molecular dynamics simulations.

Natural deep eutectic solvents (NADES) are gaining significant attention in analytical chemistry due to attractive physico-chemical properties associated with sustainable aspects. They have been successfully evaluated in different fields, and applications in sample preparation have increased in the last years. However, there is a limited knowledge related to chemical interactions and mechanism of intermolecular action with specific analytes. In this regard, for the first time, this study exploited a computational investigation using molecular dynamics (MD) predictions combined with experimental data for the extraction/determination of steroidal hormones (estriol, β-estradiol, and estrone) in urine samples using NADES. The ultrasound-assisted liquid-liquid microextraction (UALLME) approach followed by high-performance liquid chromatography with diode array detection (HPLC-DAD) was employed using menthol:decanoic acid as extraction solvent. Experimental parameters were optimized through multivariate strategies, with the best conditions consisting of 3min of extraction, 150 μL of NADES, and 3mL of sample (tenfold diluted). According to molecular dynamics predictions confirmed by experimental data, a molar ratio that permitted the highest efficiency consisted of menthol:decanoic acid 2:1 v/v. Importantly, computational simulations revealed that van der Waals interactions were the most significant contributor to the interaction energy of analytes-NADES. Using the optimized conditions, limits of detection (LOD) ranged from 3 and 8μg L-1, and precision (n = 3) varied from 8 to 19%. Intraday precision was evaluated at 3 concentrations: low (LOQ according to each analyte), medium (100μg L-1), and high (750μg L-1). Accuracy was successfully assessed through recoveries that ranged from 82 to 98%. In this case, molecular dynamics simulations proved to be an important tool for in-depth investigations of interaction mechanisms of DES with different analytes.

Study on the Interactive Mechanism between Racism and Terrorism in Europe

Given the growing racial and religious tensions in Europe and the frequent occurrences of terrorist activities, studying the correlation between the two can provide a theoretical basis for preventing terrorist activities. This study aims to explore the logical relationship and interaction mechanism between them. Taking the Paris terrorist attack in 2015 as an example, adopting the analytical dualism theory, this paper analyzes the mutual influence paths between racial discrimination and terrorist activities and discusses from cultural and structural perspectives the conditions under which racism becomes the hotbed for extremism, as well as the ways terrorist organizations manipulate racial issues to expand influence. The study concludes that racial divides in Europe provide a real basis for the spread of extremism, while extremist organizations also manipulate racial, customary, and religious emotions through online and offline means to expand influence, and the two reinforce each other. To thoroughly break this vicious cycle, positive multicultural identity needs to be promoted, structural discrimination between races needs to be eliminated at the social system level, and the independent thinking abilities and subjectivity of minority ethnic groups need to be enhanced to block the conduction of resentful emotions towards terrorism at its root.

Dynamic in situ detection in iRhizo-Chip reveals diurnal fluctuations of Bacillus subtilis in the rhizosphere

Effective colonization by microbe in the rhizosphere is critical for establishing a beneficial symbiotic relationship with the host plant. Bacillus subtilis, a soil-dwelling bacterium that is commonly found in association with plants and their rhizosphere, has garnered interest for its potential to enhance plant growth, suppress pathogens, and contribute to sustainable agricultural practices. However, research on the dynamic distribution of B. subtilis within the rhizosphere and its interaction mechanisms with plant roots remains insufficient due to limitations in existing in situ detection methodologies. To achieve dynamic in situ detection of the rhizosphere environment, we established iRhizo-Chip, a microfluidics-based platform. Using this device to investigate microbial behavior within the rhizosphere, we found obvious diurnal fluctuations in the growth of B. subtilis in the rhizosphere. Temporal dynamic analysis of rhizosphere dissolved oxygen (DO), pH, dissolved organic carbon, and reactive oxygen species showed that diurnal fluctuations in the growth of B. subtilis are potentially related to a variety of environmental factors. Spatial dynamic analysis also showed that the spatial distribution changes of B. subtilis and DO and pH were similar. Subsequently, through in vitro control experiments, we proved that rhizosphere DO and pH are the main driving forces for diurnal fluctuations in the growth of B. subtilis. Our results show that the growth of B. subtilis is driven by rhizosphere DO and pH, resulting in diurnal fluctuations, and iRhizo-Chip is a valuable tool for studying plant rhizosphere dynamics.

Emulsions co-stabilized by Polygonatum sibiricum saponin and soy protein isolate: Physical stability, interaction mechanism, interface behavior

This study investigates the interaction mechanism between Polygonatum sibiricum saponin (PSS) and soy protein isolate (SPI) to enhance the stability of oil-in-water emulsions, laying the foundation for an efficient PSS delivery system. Initially, we evaluated the stability of oil-in-water emulsions with various PSS concentrations (0.1%, 0.2%, 0.3%, 0.5%, and 1% w/w). Results indicated that PSS enhances emulsion stability by increasing absolute zeta potential, reducing average particle size, and improving resistance to external factors. Notably, concentrations of 0.3%, 0.5%, and 1% (w/w) PSS show significant improvements in emulsion stability (p < 0.05). Subsequently, we elucidated the mechanism by which PSS enhances stability. Our findings reveal that PSS interacts with SPI, inducing structural modifications in SPI and expanding its hydrophobic regions. Additionally, PSS forms SPI-PSS complexes through hydrogen bonding with aromatic amino acid residues in SPI, thereby reducing interfacial tension and maintaining stable viscoelasticity. Comparative analysis of Lissajous plots identifies the optimal PSS to SPI ratio as 0.3% (w/w) each, resulting in a resilient interface film formed by numerous SPI-PSS complexes capable of withstanding compression or extension. Overall, our study underscores the efficacy of PSS in navigating the emulsion system and collaborating with SPI to stabilize emulsions.

A Study on the Binding Mechanism and the Impact of Key Residue Mutations between SND1 and MTDH Peptide through Molecular Dynamics Simulations.

Metastasis of breast cancer is the main cause of death for patients with breast cancer. The interaction between metadherin (MTDH) and staphylococcal nuclease domain 1 (SND1) plays a pivotal role in promoting breast cancer development. However, the binding details between MTDH and SND1 remain unclear. In this study, we employed all-atom molecular dynamics simulations (MDs) and conducted binding energy calculations to investigate the binding details and the impact of key residue mutations on binding. The mutations in key residues have not significantly affected the overall stability of the structure and the fluctuation of residues near the binding site; they have exerted a substantial impact on the binding of SND1 and MTDH peptide. The electrostatic interactions and van der Waals interactions play an important role in the binding of SND1 and the MTDH peptide. The mutations in the key residues have a significant impact on electrostatic and van der Waals interactions, resulting in weakened binding. The energy contributions of key residues mainly come from the electrostatic energy and van der Waals interactions of the side chain. In addition, the key residues form an intricate and stable network of hydrogen bonds and salt-bridge interactions with the MTDH peptide. The mutations in key residues have directly disrupt the interactions formed between SND1 and MTDH peptide, consequently leading to changes in the binding mode of the MTDH peptide. These analyses unveil the detailed atomic-level interaction mechanism between SND1 and the MTDH peptide, providing a molecular foundation for the development of antibreast cancer drugs.

Comparative analysis of the interaction mechanism of γ-globulin and hemoglobin with spherical and rod-shaped gold nanoparticles

The interaction mechanism of spherical gold nanoparticles (AuNPs) and rod-shaped gold nanoparticles (AuNRs) with γ-globulin and hemoglobin was comprehensively and comparatively analyzed. γ-Globulin and hemoglobin have high affinity with AuNPs, and with two different types of binding sites on AuNRs surface. Except hemoglobin interaction with the first binding site of AuNRs, the interaction between γ-globulin/hemoglobin and AuNPs/AuNRs is the spontaneous, endothermic and entropy-driven process, and hydrophobic interaction plays a dominant role. The molecular adsorption mechanism of γ-globulin/hemoglobin on AuNPs and AuNRs surface conforms to Langmuir model and Freundlich model, respectively. The kinetic molecular mechanism between them conforms to the pseudo-second-order model, and chemisorption is the rate-limiting step. AuNPs result in the loosening and unfolding of γ-globulin backbone. AuNRs have no significant effect on γ-globulin backbone. AuNPs/AuNRs result in no significant changes in hemoglobin structure and heme group microenvironment. AuNPs/AuNRs decrease the hydrophobicity of Trp microenvironment of γ-globulin, but there is an intramolecular energy transfer from Trp residue to Tyr residue of hemoglobin. The β-sheet of γ-globulin and the α-helix of hemoglobin reduce by increasing concentrations of AuNPs/AuNRs. Molecular docking is suggesting that the specific amino acid residues of γ-globulin and hemoglobin interaction with AuNPs/AuNRs, and validates the experimental results.

Effects of volatile fatty acids on soil properties, microbial communities, and volatile metabolites in wheat rhizosphere of loess

The Loess Plateau faces critical challenges due to soil degradation. In this context, using volatile fatty acids (VFAs) from biowaste as readily available soil conditioners offer promising sustainable solutions to restore soil quality and enhance agricultural productivity. The study examined how applying different VFAs as soil amendments in arid and high-salt loess soil affected wheat plant growth, soil properties, soil microbial community diversity, volatile metabolites in soil and root exudate. The non-targeted analysis was used to identify and classify 49 soil volatile organic compounds (VOCs) and 63 root exudate VOCs to seek further specific functional volatile metabolites and explore the interaction mechanisms among plants, microorganisms, and soil. The results showed that acetic acid increased soil EC by 21.0% and decreased soil organic matter by 14.4%. Propionic acid reduced soil organic matter by 14.7%. Valeric acid increased the average root diameter by 15.1%. Further analysis revealed that rhizosphere bacterial communities, but not fungal communities, showed greater sensitivity to VFAs application. Bacterial α diversity was significantly reduced in the acetic acid treatment. The main contribution of VOCs in soil with acetic acid and propionic acid applications was alcohol, and its relative percentage was 50.06% and 43.54%, respectively, which has a significantly negative correlation with the α diversity of soil bacteria. On the contrary, the content of acylamides in soil with butyric acid and valeric acid applications was higher and significantly positively correlated with the average root diameter. It was concluded that soil microbial communities respond rapidly to acetic acid, propionic acid, butyric, and valeric acid applications by adjusting the concentration of alcohols and acylamides as secondary metabolites, respectively. This study revealed the close relationship between VFAs application type and soil properties, soil microbial community diversity, soil VOCs, and root exudates VOCs. VFAs derived from biowaste will contribute to restoring loess soil quality and achieving sustainable agriculture.

Integrating ecosystem services trade-off, drivers and zoning into watershed water environment management in Nansihu Lake Basin, China

A series of ecosystem services (ESs) have a significant impact on water environment. How these ESs can be integrated into water environment management in the lens of coupled human and natural system (CHANS) is still lack exploration. This study proposes an integrating framework that connects the ESs with water environment management to facilitate the watershed sustainable development. We employ the InVEST model to evaluate typical ESs in the Nansihu Lake Basin (largest freshwater lake in Shandong, China), and analyze the spatiotemporal characteristics and trade-off of multiple ESs indicators. By revealing the interaction mechanism and key drivers of ESs and conducting ecological functional zoning, we investigate how ESs can facilitate water environment management in the Nansihu Lake Basin. The results indicated that: (1) The high-value areas of agricultural supply service are mainly distributed in the western plain area of the basin, while high-value areas of water provision, water purification and soil conservation services are in the mountainous and hilly areas in the eastern part of the basin. (2) There is a significant trade-off between crop supply service and water purification services. Crop and livestock supply services have a greater effect on water purification services (TN) than other services. (3) Crop area sown, total power of agricultural machinery and fertilizer application are the main drivers of water purification services (TN). (4) The basin can be divided into three ecological function zones, the agricultural production zone, the ecological regulation zone and the ecological redline zone. These findings imply that water environment management should be integrated with ESs by strengthening intersectoral collaboration, conducting zoning management in watershed planning and applying differentiated control measures in each zone. This includes optimizing the scale and structure of agriculture, and implementing circular economy and clean production practices. This study explored a comprehensive framework of integrating ESs into water environment management to facilitate the sustainable development of watershed.

Investigation of interaction mechanism between polyvinyl chloride microplastics and phthalate acid esters using APGC-MS/MS

Phthalate acid esters (PAEs) are a kind of typical endocrine disruptors chemicals (EDCs). PAEs can be enriched, migrated and released into organisms through microplastics (MPs), causing high toxicological risks. This study presented an atmospheric pressure gas chromatography-tandem mass spectrometry (APGC-MS/MS) method for 10 PAEs trace analysis. Based on this method, the interaction mechanism between polyvinyl chloride microplastics (PVC MPs) and PAEs was explored. The established APGC-MS/MS method achieved 10 PAEs analysis in 14 min with the satisfied detection limit as low as 0.0025 μg/L and excellent linearity (R2 = 0.99868–0.99996). The interaction mechanism investigation showed that PVC MPs had high adsorption and desorption capacities for PAEs. The adsorption mechanism involves adsorption distribution, surface adsorption, hydrophobic interaction and intermolecular van der Waals force. Temperature, diffusion channels, pore filling, hydrophobicity and solubilization may be potential desorption mechanisms. Moreover, the intestinal environment of warm-blood organisms has the highest bioavailability of PAEs. Overall, this APGC-MS/MS method of PAEs had the virtue of simplicity, efficiency, reliability and sensitivity, and could serve as a potential tool for risk analysis of MPs and PAEs exposure.

Lubrication antagonism mechanism of nano-MoS2 and soot particles in ester base oil

Spherical nano-MoS2 (S-MoS2) has excellent lubricating properties and potential application value in engine oil additives. Engine soot can enter the engine oil, so the tribological interaction between S-MoS2 and diesel combustion soot (DCS) should be investigated. In this study, DCS was used to simulate engine soot. The interaction was investigated in dioctyl sebacate (DOS), and the interaction mechanism was full characterized. Results showed that S-MoS2 and DCS had obvious antagonism effects on lubrication. The 0.5% S-MoS2 exhibited good lubricating properties in DOS, which could reduce friction by ∼22% and wear by ∼54%. However, after 0.5% S-MoS2 was added to the 0.5% DCS contaminated DOS, the lubrication performance was not improved and was even worse than that without S-MoS2. When S-MoS2 was added for DOS lubrication, a tribofilm containing MoS2 formed on the friction surface, but simultaneously adding 0.5% DCS resulted in the disappearance of the MoS2 tribofilm. Moreover, under the action of friction heat, DCS and S-MoS2 could form hard MoxCy, thereby increasing abrasive wear. Finally, a preliminary deantagonism method was provided. After 2.0% zinc isooctyl dithiophosphate was added to the above antagonistic system, the friction coefficient did not show visible changes, but the wear recovered to a level close to that when only S-MoS2 was added. The antiantagonism method is not very satisfactory and some more efficient methods need to be further explored.

Multi-dimensional modeling of solitary wave–structure interaction problems by using a [formula omitted]-LES-SPH model

The interaction mechanisms between waves and marine structures are a popular research topic. This paper applies the weakly compressible smoothed particle hydrodynamics (WCSPH) method to study the dynamics of green water overtopping. To enhance the accuracy of the simulations, the SPH method coupled with the large eddy simulation (LES) model is employed for numerical investigations. Initially, we validate the effectiveness of the model by simulating the generation of solitary waves and irregular waves, as well as numerically reproducing the water surface morphology during the interaction between solitary waves and the deck. Subsequently, the validated model is used to study the dynamic characteristics of different types of waves overtopping, revealing significant variations in their motion. Furthermore, we investigate the effect of deck roughness during the entire green water overtopping process in terms of both protrusions extent and distribution, confirming that a reasonable setting of the protrusions can greatly reduce the wave impact loads on the deck, thereby protecting the structure. Additionally, a three-dimensional model is developed to study the green water problem, and we find that the turbulence phenomenon is more pronounced in the three-dimensional scenario.

Unraveling the interactive effects of Na2O/Al2O3, SiO2/Al2O3 and calcium on the properties of geopolymers from circulating fluidized bed fly ashes

Circulating fluidized bed fly ash (CFB-FA), generated as solid waste from the thermal power plants with different contents of calcium. The reuse of CFB-FA for construction materials is the most promising method for the large-scale transformation of waste to resource. This paper examines the ratio effects of Na2O/Al2O3 and SiO2/Al2O3 on geopolymers from low-calcium fly ash (CFB-FA1) and high-calcium fly ash (CFB-FA2) by using a mixture of Na2SiO3 and NaOH as the alkali activator. The detailed mechanistic study with XRD, FTIR, SEM, and MAS NMR is also conducted for the roles of silicon, aluminum, and calcium in the reaction process and their mutual interaction mechanism, along with the regulating mechanism for the compressive strength and setting time of geopolymers. The results indicate that the increased ratios of Na2O/Al2O3 and SiO2/Al2O3 are favorable for the reactions and reduce the setting time of CFB-FA1 and CFB-FA2 based geopolymer. In CFB-FA1, the higher silicon and aluminum content is conducive to their dissolution by regulating the Na2O/Al2O3 ratio, forming N-A-S-H and resulting in the increased strength. A small amount of calcium mainly exists in the form of CaSO4, which completely participates in the reaction. In CFB-FA2, the silicon and aluminum contents are relatively low, while the calcium content is high. The compressive strength is achieved by regulating the SiO2/Al2O3 ratio to increase the dissolution of silicon and aluminum, allowing CaSO4 and CaO to react and form C-A-S-H and ettringite, with CaCO3 as unreactive. The low calcium is favorable for the long-term strength, but the high calcium acts oppositely, primarily attribute to the decomposition of ettringite, a critical component for maintaining the compressive strength of CFB-FA2 based geopolymers.

Prenylated Flavanone Enantiomers with α-Glucosidase Inhibitory Activity from the Root Bark of Morus alba.

A focused chemical investigation into the polar fractions of a well-known traditional Chinese medicine called Sang-Bai-Pi (the root bark of Morus alba) yielded a panel of prenylated flavanones. The new compounds were identified as four pairs of enantiomers (1a/1b-4a/4b) featuring the same constitution structure, on the basis of HRMS, NMR and ECD analyses. Several previously reported known racemic co-metabolites were also analyzed and separated by HPLC on chiral columns, and the absolute configurations of pure enantiomers were established via ECD technique for the first time. The inhibition of these isolates against the antidiabetic target α-glycosidase was further tested, with most of them showing decent inhibitory activity compared with the positive control acarbose. The interaction mechanism of two selected compounds (3a & 4b) was explored by kinetics experiment, which revealed a mixed type of inhibition pattern toward the enzyme.

Novel Guanidinium-Functionalized Stigmasterol for Bile Salt Binding and Serum Cholesterol Reduction: Synthesis, Interaction Mechanisms, and In Vivo Function.

A novel amphiphilic guanidyl-functionalized stigmasterol hydrochloride (GFSH) was designed and synthesized as bile salt sequestrants for cholesterol reduction. GFSH exhibited a considerable in vitro capacity for bile salt binding in gastrointestinal digestion and alleviated hypercholesterolemia in vivo. GFSH spontaneously interacted with sodium cholate via synergistic electrostatic, hydrophobic, and hydrogen-bonding interactions. The effects of GFSH on serum cholesterol reduction in mice fed a high-fat-high-cholesterol diet were explored by measuring the expression of key transcription factors related to bile acid metabolism. GFSH produced a dose-dependent reduction in weight gain, hepatic fat accumulation, and fecal and blood markers. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analyses demonstrated GFSH-induced expression of hepatic CYP7A, LXRα, and LDL-R. GFSH exerts the cholesterol-lowering activity by inducing the bile acid metabolism.

Novel sulfonylurea fluorescence probes for antiproliferative activity, detection and imaging of fluoride ions in living cells

In this study, four novel triphenylpyrazoline 4-toluenesulfonylureas (PYSUs) were synthesized to develop potential anticancer drugs and fluorescent probes for the detection of F− ions. The compounds were synthesized via a two-step microwave-assisted method. The antiproliferative activity of the PYSUs was tested against two cancer cell lines: HepG2 and MDA-MB-231. Among the compounds, 3a exhibited strong activity against both cell lines, while 3b showed strong activity against MDA-MB-231 cells but weaker inhibition of HepG2 cells. Furthermore, compound 3b was identified as the best fluorescent probe, with an increase in emission intensity in the presence of F− ions from tetrabutylammonium fluoride (TBAF). In DMSO, the emission wavelength was found to be 518 nm (green) with an excitation wavelength of 469 nm. The limit of detection (LOD) was calculated to be 0.269 mM in the linear range of 5–10 mM. The interaction mechanism between F− ions and compound 3b was further explored via DFT/TDDFT calculations. Additionally, fluorescent imaging of TBAF-incubated MDA-MB-231 and HepG2 cells confirmed the potential of PYSUs as fluorescent sensors for F− ions in living cancer cells.

Evaluation of inhibition effect and interaction mechanism of antiviral drugs on main protease of novel coronavirus: Molecular docking and molecular dynamics studies

The outbreak of pneumonia caused by the novel coronavirus (SARS-CoV-2) has presented a challenge to public health. The identification and development of effective antiviral drugs is essential. The main protease (3CLpro) plays an important role in the viral replication of SARS-CoV-2 and is considered to be an effective therapeutic target. In this study, according to the principle of drug repurposing, a variety of antiviral drugs commonly used were studied by molecular docking and molecular dynamics (MD) simulations to obtain potential inhibitors of main proteases. 24 antiviral drugs were docked with 5 potential action sites of 3CLpro, and the drugs with high binding strength were further simulated by MD and the molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) binding free energy calculations. The results showed that the drugs with high flexibility could bind to 3CLpro better than those with low flexibility. The interaction mechanism between antiviral drugs and main protease was analyzed in detail by calculating the root mean square displacement (RMSD), root mean square fluctuation (RMSF) and interaction residues properties. The results showed that the six drugs with high flexibility (Remdesivir, Simnotrelvir, Sofosbuvir, Ledipasvir, Indinavir and Raltegravir) had strong binding strength with 3CLpro, and the last four antiviral drugs can be used as potential candidates for main protease inhibitors.

An investigation on pyrite floatability using stable micro-nanobubble-assisted flotation

This study critically examines the impact of micro-nanobubble (MNB)-assisted flotation on pyrite recovery in bulk ore, and clarifies the intricate relationship between pyrite and its associated ore. The physicochemical properties of MNBs and the interaction mechanisms between xanthate collector and pure pyrite mineral were evaluated using advanced analytical techniques, including Dynamic Light Scattering (DLS), Field-Emission Scanning Electron Microscopy coupled with Energy-Dispersive X-ray Spectroscopy (FESEM-EDX), and Ultraviolet-Visible Spectroscopy (UV-Vis), in the absence and the presence of MNBs. MNBs were created through hydrodynamic cavitation, and their characteristics revealed a size increase from 600 nm to 3 µm over 25 days. Notably, the zeta potential measurements indicated an increase from -2.5 to 0 mV at a constant pH of 8, correlating with the geometric mean size of MNBs coarsening from 600 nm to 2-3 µm. The FESEM and EDS analyses disclosed that ultrasonic treatment effectively dispersed ultrafine surface coatings on pyrite particles, increasing iron and sulfur purity by 8% and 6%, respectively, and significantly reducing surface oxygen by 53%. Micro-flotation and batch rougher kinetic flotation experiments were conducted with and without MNBs, leading to a 7% and 8% improvement in recovery for pyrite mono-minerals (-105+53 µm) and its ore (d&lt;sub&gt;80&lt;/sub&gt;=150 µm), respectively. The sorption behavior of sodium isopropyl xanthate (SIPX) collector on the particle surface was also investigated at various concentrations (ca. 10-160 µM) in the presence and absence of stable MNBs and demonstrated that the presence of MNBs resulted in a 1.6-fold increase in collector absorption on the pyrite surface, confirming the findings obtained from micro-flotation. Moreover, adsorption behavior is up to 1.3 times compared to the scenario without MNBs. The adsorption process was controlled by a pseudo-second-order model, indicating a chemical sorption mechanism.

Mechanistic Regulation of Epidermal Growth Factor and Hormonal Receptors by Kinase Inhibitors and Organofluorines in Breast Cancer Therapy.

Differential expression patterns of growth factor (EGFR, HER-2) and hormonal (ER, PR) receptors in breast cancer (BC) remain crucial for evaluating and tailoring therapeutic interventions. This study investigates differential expression profiles of hormonal and growth factor receptors in BC patients and across age groups, major subclasses, disease stages and tumor histology and survival rates, the efficacy of emerging clinical trial drugs (Dabrafenib and Palbociclib) and elucidating their molecular interaction mechanisms for efficient therapeutic strategies. Gene and protein expression analysis in the normal vs BC and across age groups and major subclasses reveals divergent patterns as EGFR and HER-2 levels are reduced in tumors versus normal tissue, while ER and PR levels are higher, particularly in luminal subtypes. However, there was no significant difference in survival rates among high and low/medium expression levels of EGFR and PR receptors. Conversely, patients with high HER-2 and ER expression exhibited poorer survival rates compared to low or medium expression levels. The in vitro findings indicate that Dabrafenib exhibits greater effectiveness than Palbociclib in suppressing various BC cells such as MCF-7 (Luminal), MDA-MB-231 (Triple-Negative), SKBR-3 (HER-2 + ) proliferation, promoting cell death, (IC50 of Dab < Pal) at 24 and 48 h, ROS production, and reduced ER and PR, elevated HER-2 with no change in EGFR expression. Molecular simulation studies revealed Dabrafenib's thermodynamically stable interactions (ΔG), tighter binding, and less structural deviation in the order EGFR > HER-2 > ER > PR as compared to Palbociclib (HER-2 > ER > PR = EGFR). These results indicate that Dabrafenib, compared to Palbociclib, more effectively regulates breast cancer cell proliferation through specific interactions with hormonal and growth factor receptors towards a repurposing approach.

Imaging and proteomics toolkits for studying organelle contact sites.

Organelle contact sites are regions where two heterologous membranes are juxtaposed by molecular tethering complexes. These contact sites are important in inter-organelle communication and cellular functional integration. However, visualizing these minute foci and identifying contact site proteomes have been challenging. In recent years, fluorescence-based methods have been developed to visualize the dynamic physical interaction of organelles while proximity labeling approaches facilitate the profiling of proteomes at contact sites. In this review, we explain the design principle for these contact site reporters: a dual-organelle interaction mechanism based on how endogenous tethers and/or tethering complexes localize to contact sites. We classify the contact site reporters into three categories: (i) single-protein systems, (ii) two-component systems with activated reporter signal upon organelle proximity, and (iii) reporters for contact site proteomes. We also highlight advanced imaging analysis with high temporal-spatial resolution and the use of machine-learning algorithms for detecting contact sites.

Influencing the powder particle transport in high-speed laser melt injection

Using high-speed laser melt injection (HSLMI), it is possible to generate wear-resistant metal matrix composite (MMC) surfaces on tools with great productivity. Since high laser intensities are required for reaching high process speeds, strong interactions can occur between powder particles and the laser beam. In order to reduce the interaction time and gain a better understanding of the role of particle transport in the HSLMI process, trajectories of spherical fused tungsten carbide (SFTC) particles were analyzed using high-speed imaging. The trajectories were divided into a path outside the laser beam and a path inside the laser beam. The identified interaction mechanisms were particle deformations, the formation of agglomerates, and particle disintegration. The volume flow rate of the feeding gas was found to have a decisive influence on the travel time of the particles, whereas the powder feed rate and the working distance of the powder nozzle only had a minor influence. Consequently, an increased volume flow rate led to a significant reduction of interactions between SFTC particles and the laser beam.