Search Results (358)

Significance: This study addresses critical industrial and biomedical applications including glass blowing (thermal management of shrinking sheets), polymer sheet extrusion (controlled cooling), magnetic drug delivery (nanoparticle targeting), and nuclear reactor cooling (enhanced heat transfer). Aim: We present a novel nonlinear analysis of magnetohydrodynamic (MHD) boundary layer flow of a Jeffery Al₂O₃ nanofluid over a shrinking permeable plate with convective boundary conditions, uniquely integrating mixed convection, Ohmic dissipation, heat generation, Brownian motion, and thermophoresis within a non-Newtonian nanofluid framework. Methodology: The governing partial differential equations are transformed using similarity transformations and solved via the Adomian decomposition method (ADM). Comprehensive validation against RK4, RK45, and bvp4c demonstrates excellent agreement with maximum relative errors below $5\times {10}^{-4}$. Key Contribution: (i) Normal velocity decreases by 15–25% as the Biot number increases from $Bi=0.4$ to $0.6$; (ii) tangential velocity decreases by 20–30% as the magnetic parameter increases from $M=5$ to 15; (iii) temperature increases by 30–40% as the Eckert number increases from $Ec=0.5$ to $2.5$; (iv) ADM converges within 12–15 terms with $L_2$ errors $<{10}^{-5}$; (v) skin friction coefficient increases from $C_f=3.02713$ to $3.90082$ as $Q_0$ increases from 1 to 4; (vi) Nusselt number values: $Nu/\sqrt{Re}=0.4621$ at $Pr=0.7$, $0.8954$ at $Pr=2$, $3.2890$ at $Pr=20$. These quantitative findings provide design guidelines for engineers in thermal management and biomedical applications. Full article

Background/Objectives: The most abundant flavonoid, quercetin, which is mostly found as glycosides, is widely distributed in plants. Quercetin is rapidly metabolized, having a short half-life in the blood circulation, and forms its conjugates by undergoing ring cleavage of the benzopyranone ring system. Despite its fast clearance in the body, quercetin was demonstrated to have clinically anti-inflammatory, cardioprotective, antidiabetic, and anti-obesity activities. This study aimed to determine whether quercetin itself or its metabolites are responsible for these activities. Methods: We performed molecular docking of 27 metabolites, including quercetin itself, against ten inflammation-related proteins in silico. We then conducted microscale thermophoresis (MST) of selected metabolites towards the NLRP3 inflammasome. Results: Overall, Phase II metabolites yielded better binding energies compared to the metabolites formed by degradation. MST results revealed that isorhamnetin, the 4-O-methylated metabolite of quercetin, gave the best results, with a binding affinity (K_D value) of 16.12 ± 5.16 µM, even better than quercetin itself, which has a binding affinity of 44.84 ± 4.21 µM. Glucuronide metabolites of quercetin (isorhamnetin 3-O-glucuronide, quercetin 7-O-glucuronide, and quercetin 3-O-glucuronide) were found to bind to the inflammasome protein with low binding affinities, whereas small degradation products (hippuric acid and 3,4-dihydroxytoluene) did not bind at all. Conclusions: These results suggest that Phase II metabolites, specifically isorhamnetin, may contribute more significantly to the biological activity of quercetin than the parent compound, however, degradation products appear inactive. Full article

This study presents a numerical investigation of the laminar forced convection of polyethylene glycol-based nanocolloids within a horizontal pipe. To bridge the gap between theoretical predictions and practical performance, simulations were conducted over a Reynolds number range of 500 to 2000, utilizing a model validated against laboratory-scale experimental data and well-defined boundary conditions. Our analysis focuses on the thermal behavior of polyethylene glycol 200 enriched with metal oxide nanoparticles and multi-walled carbon nanotubes, which were selected for their capacity to enhance thermal conductivity while maintaining manageable viscosity. The results demonstrate that PEG 200-based nanocolloids significantly improve heat transfer performance in the laminar regime. This enhancement is attributed to the superior intrinsic thermal properties of the nanoparticles and the complex synergistic interactions—such as Brownian motion and thermophoresis—between the particles and the PEG base fluid. A critical evaluation of the standard approach of incorporating thermophysical properties into the numerical approach led to significant discrepancies in flow predictions. Additionally, our study establishes that assuming constant thermophysical properties during the heating process introduces simulation errors exceeding 10%. These findings underscore the necessity of incorporating temperature-dependent, experimentally validated data into numerical models to ensure predictive accuracy. Ultimately, this work advocates for a nuanced approach to nanocolloid design that prioritizes the specific chemical and rheological compatibility between nanoparticle types and the base fluid. Full article

This study introduces an efficient and accurate two-stage explicit computational scheme for solving partial differential equations (PDEs) containing first-order time derivatives. The suggested method is a modification of the classical Runge–Kutta scheme that introduces a new first-stage formulation. This minimizes numerical error with moderate step sizes while preserving the stability region of the classical method. Spatial discretization is performed using a sixth-order compact finite-difference scheme to obtain high-resolution solutions. The analysis of stability and convergence is strictly determined for both scalar and system forms of convection–diffusion-type equations. To illustrate the suitability of the method, a dimensionless mathematical model of the unsteady, incompressible, laminar flow of a Prandtl-type non-Newtonian nanofluid over a Riga plate is considered, accounting for viscous dissipation, thermophoresis, Brownian motion, and a magnetic field. Here, the Prandtl ternary nanofluid is defined as a non-Newtonian nanofluid that follows the Prandtl rheological model, and it exhibits three critical transport phenomena: heat conduction, viscous dissipation, and nanoparticle diffusion. Representative values of the Prandtl number $P_r=3$ and Reynolds number $R_e=5$ are used to perform the simulation, and other parameters, including but not limited to the Hartmann number $H_a$, Williamson number $W_e$, thermophoresis $N_t$ and Brownian motion $N_b$, are varied to evaluate the flow behavior. Moreover, an artificial neural network (ANN)-developed surrogate model is used to calculate the skin friction coefficient and the local Sherwood number, using five input parameters: the Reynolds number, Prandtl number, Schmidt number, Brownian motion parameter, and thermophoresis parameter. The governing partial differential equations yield high-fidelity numerical data used to train the surrogate model. The data is split into 80% for training, 10% for validation, and 10% for testing. The ANN is tested using regression analysis and error histograms, which demonstrate high accuracy and generalization capacity. Numerical simulation combined with AI-based prediction is a cost-efficient method for real-time estimation of complex non-Newtonian nanofluid systems. Full article

This is a review article that covers the history of the development of the equation of motion for solid particles in fluids, starting with the early work, before the Navier–Stokes equations were developed. Particular emphasis is placed on the development of the transient equation of motion, which features the history (or memory) term and the added mass (virtual mass) term. The salient features of the equation and the methods of their derivation are pointed out. Creeping, non-inertia flows as well as advective flows are surveyed, with particular emphasis on their effects on the functional form of the history term. Modifications to the hydrodynamic force due to possible interface slip are also examined. The review also deals with the inclusion of the weaker lateral (lift) forces and the inclusion of the effects of Brownian movement, which gives rise to thermophoresis—an important source of nanoparticle movement and surface deposition. The drag on irregularly shaped particles—another important feature of nanoparticles—is also examined. The review concludes with a short section on significant unknown issues and work that may be carried out in the near future for the theoretical and computational development of the subject. Full article

An analysis is presented for the steady thermophoresis and photophoresis of a homogeneous dispersion of identical aerosol spheres of typical physical properties and surface characteristics. The analysis assumes a moderately small Knudsen number (less than about 0.1), such that the gas motion lies within the slip-flow regime, including thermal creep, temperature jump, thermal stress slip, and frictional slip at the particle surfaces. Under conditions of low Peclet and Reynolds numbers, the coupled momentum and energy equations are analytically solved using a unit cell approach that explicitly incorporates interparticle interactions. Closed-form expressions are derived for the mean particle migration velocities in both thermophoresis driven by a uniform temperature gradient and photophoresis induced by an incident radiation field. The results reveal that the normalized particle velocities, referenced to those of an isolated particle, generally decrease with increasing particle volume fraction, though exceptions occur for thermophoresis. While thermal stress slip and thermal creep exert no influence on the normalized thermophoretic velocity, they markedly affect the normalized photophoretic velocity, which rises with the thermal stress slip to the thermal creep coefficient ratio. For both phenomena, the normalized migration velocities increase monotonically with the particle-to-fluid thermal conductivity ratio. Full article

The p53 tumor suppressor, a key transcription factor, acts as a cellular stress sensor that regulates hundreds of genes involved in responses to DNA damage, oxidative stress, and ischemia. Through these actions, p53 can arrest cell cycle, initiate DNA repair, or trigger cell death. In addition to its nuclear functions, p53 can translocate to mitochondria to promote apoptosis. Studies using isolated mitochondria have suggested that p53 drives the voltage-dependent anion channel (VDAC1) into high molecular mass complexes to mediate apoptosis. VDAC1 is a central regulator of cellular energy production and metabolism and also an essential player in apoptosis, induced by various apoptotic stimuli and stress conditions. We previously demonstrated that VDAC1 oligomerization, induced by various apoptosis stimuli and stress conditions, forms a large pore that enables cytochrome c release from mitochondria, thereby promoting apoptotic cell death. In this study, we show that p53 interacts with VDAC1, modulates its expression levels, and promotes VDAC1 oligomerization-dependent apoptosis. Using purified proteins, we found that p53 directly binds VDAC1, as revealed by microscale thermophoresis and by experiments using bilayer-reconstituted VDAC1, in which p53 reduced VDAC1 channel conductance. Furthermore, overexpression of p53 in p53-null cells or in cells expressing wild-type p53 increased VDAC1 expression and induced VDAC1 oligomerization even in the absence of apoptotic stimuli. Together, these findings identify VDAC1 as a direct p53 target whose expression, oligomerization, and pro-apoptotic activity are regulated by p53. They also reinforce the central role of VDAC1 oligomerization in apoptosis. Full article

Background: Atherosclerosis (AS) serves as the primary pathological basis for cardiovascular disease-related deaths worldwide, posing a severe threat to public health security. Heat shock protein 90 (HSP90) plays a crucial regulatory role in the pathological progression of AS, emerging as a potential target for anti-atherosclerosis drug development in recent years. Calenduloside E (CE) is a pentacyclic triterpenoid saponin isolated from Aralia elata (Miq.) Seem. Previous studies have confirmed its anti-atherosclerotic activity, but its weak efficacy and narrow therapeutic index limit its clinical application. In this study, the CE scaffold was hybridized with a ticagrelor-derived fragment to enhance anti-atherosclerotic activity. In this study, the CE scaffold was hybridized with a ticagrelor fragment to achieve improved activity. Methods: Based on the principle of molecular hybridization, CE was linked to the active fragment of ticagrelor via a PEG chain. Ten CE derivatives were synthesized by modifying the sugar substituents. In vitro experiments were conducted to detect cytotoxicity and protective activity against ox-LDL-induced HUVECs injury. Molecular docking and Surface Plasmon Resonance (SPR) assays were used to evaluate the interaction between CE derivatives and the known target HSP90β. Combined with Microscale Thermophoresis (MST), SwissTargetPrediction, and molecular docking, other potential targets of CE derivatives were identified. Results: In the ox-LDL-induced HUVECs injury model, all compounds except C2 and C9 exhibited protective activity. Among these compounds, compound C5 exhibited the optimal protective effect, with an EC₅₀ value of 1.44 μM. Molecular docking results revealed that both C5 and CE could bind to HSP90β by forming hydrogen bonds with the key amino acid Asp93. Additionally, SPR results indicated that C5 and CE had similar binding affinities to HSP90β, with dissociation constants (K_D) of 1.73 μM and 1.72 μM, respectively. MST demonstrated that C5 binds to HSP90β with an affinity 111 times higher than that of ticagrelor. SwissTargetPrediction and molecular docking identified P2Y12 as another potential target of derivative C5. Conclusions: Compound C5 exerts protective effect against ox-LDL-induced HUVECs injury by targeting HSP90β. Its effective concentration is significantly improved compared with that of the parent CE, which provides a possibility for reducing clinical dosage and toxic side effects in subsequent studies. Furthermore, C5 may exert its effects by targeting another potential target, P2Y12, offering references for the rational design of novel anti-atherosclerotic drugs. Full article

Macrocyclic drugs are promising for targeting undruggable proteins, including those in cancer. Our prior work identified BE-43547A₂ (BE) as a selective inhibitor of pancreatic cancer stem cells in PANC-1 cultures, but its high lipophilicity limits clinical application. To address this, we designed derivatives retaining BE’s backbone while modifying tail groups to improve its properties. A concise total synthesis enabled a versatile late-stage intermediate (compound 17), serving as a platform for efficient diversification of BE analogs via modular click chemistry. This approach introduced a central triazole ring connected by flexible alkyl spacers. Key properties, including lipophilicity, solubility, and Caco-2 permeability, were experimentally determined. These derivatives exhibited reduced lipophilicity and improved solubility but unexpectedly lost cellular activity. Direct target engagement studies using MicroScale Thermophoresis (MST) revealed compound-dependent deactivation mechanisms: certain derivatives retained binding to eEF1A1 with only modestly reduced affinity (e.g., compound 29), while others showed no detectable binding (e.g., compound 31). Microsecond-scale molecular dynamics simulations and free-energy calculations showed that, for derivatives retaining target affinity, tail modifications disrupted the delicate balance of drug–membrane and drug–solvent interactions, resulting in substantially higher transmembrane free-energy penalties (>5 kcal/mol) compared to active compounds (<2 kcal/mol). These insights emphasize the need to simultaneously preserve both target engagement and optimal permeability when modifying side chains in cell-permeable macrocyclic peptides, positioning compound 17 as a robust scaffold for future lead optimization. This work furnishes a blueprint for balancing drug-like properties with therapeutic potency in macrocyclic therapeutics. Full article

Zika virus (ZIKV) caused Zika outbreaks and continues to post threats to public health. ZIKV infection may cause congenital abnormalities during pregnancy and neurological manifestations in adults. The recurrent public health threat of Zika in various geographical areas demonstrates a need for the development of effective therapeutics. Currently, there are no approved therapies for Zika. ZIKV is a single-stranded, positive-sense RNA virus, whose genome encodes three structural proteins and seven non-structural proteins. The surface envelope (E) protein is essential for host–cell recognition and viral entry; therefore, inhibition of E-mediated viral entry is a key strategy underlying antiviral treatments. Here, molecular docking-based virtual screening was used to screen small-molecule compound libraries to identify potential ZIKV entry inhibitors. Among the compounds identified, Pyrimidine-Der1 exhibited efficient inhibition of reporter ZIKV infection. The microscale thermophoresis assay confirmed its binding with the ZIKV E protein. This compound has effective inhibition of authentic ZIKV infection in a plaque inhibition assay against R103451, PAN2016, and FLR human strains (IC₅₀: ~3–5 μM). Additionally, it efficiently inhibited ZIKV infection at viral entry and fusion steps of the virus life cycle in a time-of-addition assay. Overall, Pyrimidine-Der1 is a promising ZIKV entry inhibitor, warranting further optimization and evaluation. Full article

Nucleic acid aptamers leverage defined tertiary structures for precise molecular recognition, positioning them as transformative biomedical tools. We engineered AP1-F, a G-quadruplex (G4)-structured aptamer that selectively binds membrane-anchored nucleolin (NCL) non-permeabilizing, overcoming a key limitation of conventional probes. Microscale thermophoresis confirmed nanomolar affinity to NCL. By means of rigorous optimization, AP1-F attained a greater than ten-fold fluorescence signal ratio between malignant and normal cells in co-cultures, exceeding the extensively researched AS1411. Dual-channel flow cytometry demonstrated over 98.78% specificity at single-cell resolution within heterogeneous cell populations, owing to AP1-F’s unique membrane localization—unlike AS1411’s intracellular uptake, which elicited erroneous signals from cytoplasmic NCL. Competitive binding experiments and Laser Confocal Imaging confirmed that AP1-F specifically identifies cancer cells by binding to the NCL recognition site on the membrane. In pathological sections, AP1-F exhibited a 40.5-fold fluorescence intensity ratio between tumor and normal tissue, facilitating accurate tissue-level differentiation. Significantly, it delineated molecular subtypes by associating membrane NCL patterns with morphometric analysis: luminal-like MCF-7 displayed consistent staining in cohesive clusters, whereas basal-like MDA-MB-468 revealed sporadic NCL with irregular outlines—characteristics imperceptible to intracellular-targeted antibodies, thus offering subtype-specific diagnostic insights. This combination biochemical–morphological approach accomplished subtype differentiation with a single-step, non-permeabilized process that maintained lower cytotoxicity and tissue integrity. AP1-F enhances diagnostic accuracy by utilizing spatial confinement to eradicate intracellular interference, connecting molecular specificity to intraoperative margin evaluation or biopsy categorization. Full article

Pharmacological chaperones of heterogeneous nuclear ribonucleoproteins (hnRNPs) show promise as potential neuroprotective drug candidates. They are expected to prevent the accumulation of neurotoxic hnRNP biocondensates and aggregates, which are hallmarks of severe degenerative diseases. Here, we present the first rational design of oligonucleotide chaperones of hnRNP A1. This design was inspired by previous studies on the specificity of the RNA recognition motif (RRM) and the RGG motif of hnRNP A1 for endogenous nucleic acids. To obtain robust and specific chaperones, we combined an RRM-binding sequence with an RGG-binding G-quadruplex oligonucleotide that inhibits hnRNP A1 aggregation and introduced various modifications into the sugar-phosphate backbone of the oligonucleotide. Modifications that locked the RRM-binding sequence in a conformational state characteristic of RNA improved chaperone affinity and activity. The former was assessed using microscale thermophoresis assays, while the latter was evaluated using fluorimetry and microscopy. The leading chaperone bound to hnRNP A1 at micromolar concentrations and inhibited the assembly of its condensates and amyloid-like aggregates (fibrils) by over 90%. Full article

Background: The study of non-Newtonian fluids in thin channels is crucial for advancing technologies in microfluidic systems and targeted industrial coating processes. Nanofluids, which exhibit enhanced thermal properties, are of particular interest. This paper investigates the complex flow and heat transfer characteristics of a Sutterby nanofluid (SNF) within a thin channel, considering the combined effects of magnetohydrodynamics (MHD), Brownian motion, and bioconvection of microorganisms. Analyzing such systems is essential for optimizing design and performance in relevant engineering applications. Method: The governing non-linear partial differential equations (PDEs) for the flow, heat, concentration, and bioconvection are derived. Using lubrication theory and appropriate dimensionless variables, this system of PDEs is simplified into a more simplified system of ordinary differential equations (ODEs). The resulting nonlinear ODEs are solved numerically using the boundary value problem (BVP) Midrich method in Maple software to ensure accuracy. Furthermore, data for the Nusselt number, extracted from the numerical solutions, are used to train an artificial neural network (ANN) model based on the Levenberg–Marquardt algorithm. The performance and predictive capability of this ANN model are rigorously evaluated to confirm its robustness for capturing the system’s non-linear behavior. Results: The numerical solutions are analyzed to understand the variations in velocity, temperature, concentration, and microorganism profiles under the influence of various physical parameters. The results demonstrate that the non-Newtonian rheology of the Sutterby nanofluid is significantly influenced by Brownian motion, thermophoresis, bioconvection parameters, and magnetic field effects. The developed ANN model demonstrates strong predictive capability for the Nusselt number, validating its use for this complex system. These findings provide valuable insights for the design and optimization of microfluidic devices and specialized coating applications in industrial engineering. Full article

Additives such as surfactants (Tween-20) and cryoprotectants (glycerol and trehalose) are often used in enzymatic assays to improve the quality and long-term stabilization of proteins. However, these additives can affect the enzymatic activity and the enzyme’s affinity for active compounds, such as inhibitors, and must be considered during assay design since a slight shift in enzyme behavior may compromise the reliability of the results. In this study, the effects of Tween-20, glycerol, and trehalose on hyaluronidase (Hyal) were systematically evaluated by assessing their influence both directly—through microscale thermophoresis (MST) signals of the labeled enzyme (Hyal*)—and indirectly, by monitoring the formation of the final product of the degradation of hyaluronic acid, tetrasaccharide (Tet), using capillary electrophoresis (CE/UV). Hyal was labeled for the first time with ATTO-647 NHS ester, a commercial dye compatible with MST. Efficient labeling was achieved in a phosphate-based buffer without loss of catalytic activity. Tween-20 showed no impact on MST signals nor on enzymatic performance when used between 0.005 and 0.05% (v/v). Glycerol also did not interfere with MST measurements; however, it significantly reduced catalytic activity at concentrations above 2% (v/v). Trehalose affected Hyal* fluorescence in a concentration-dependent manner and enhanced catalytic activity even at 0.02% (v/v). Full article

YKL-40 is a chitinase-like glycoprotein implicated in various pathological processes, yet its glycosaminoglycan (GAG) binding profile beyond heparin has not been examined. In this study, we performed a Microscale Thermophoresis (MST) analysis on the heparin-binding glycoprotein YKL-40 using low molecular weight GAG oligosaccharides. We identified two new GAG ligands, dermatan sulfate (DS) and hyaluronan (HA), while chondroitin sulfate (CS) showed no detectable binding affinity. The results show that heparin is bound with the strongest affinity, followed by DS and HA. To further investigate these differences, molecular docking was used to evaluate possible binding modes. Molecular docking results indicated that both heparin and DS interacted with the same site on YKL-40, the heparin-binding site at residues 143–149, suggesting a multifunctional binding region that may act as a competitive switch or integration hub for spatially regulated signaling. Together, these findings expand the known ligand profile of YKL-40 and offer new insights into its ECM-context-dependent roles, with implications for targeting YKL-40 in diseases involving chronic inflammation, fibrosis, and cancer progression. Full article