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Multidrug resistance (MDR) during clinical chemotherapy for cancer has been considered a major obstacle to treatment efficacy. The involvement of adenosine triphosphate-binding cassette (ABC) transporters in the MDR mechanism significantly reduces the efficacy of chemotherapeutics. This study investigates the potential of morin, a dietary bioflavonoid, to overcome colchicine resistance in KBChR-8-5 MDR cells. The P-gp inhibitory activity by morin was measured by calcein-AM drug efflux assay. Western blot analysis was employed to evaluate P-gp messenger RNA and protein expressions following morin treatment. Flow cytometry analysis and acridine orange/ethidium bromide fluorescence staining were utilised to investigate the induction of apoptosis and cell cycle arrest upon treatment with morin and paclitaxel in combination. Additionally, polymerase chain reaction (PCR) array analysis was conducted to study the gene expression profiles related to MDR, apoptosis and cell cycle arrest during treatment with morin, paclitaxel or their combination. Morin exhibited a strong binding interaction with human P-gp. This was corroborated by drug efflux assays, which showed a reduction in P-gp efflux function with increasing morin concentration. Furthermore, morin and paclitaxel combination potentiated the induction of apoptosis and G2/M phase cell cycle arrest. Morin treatment significantly downregulated the gene expression of ABCB1 and P-gp membrane expressions in MDR cells. Additionally, PCR array gene expression analysis revealed that the combination treatment with morin and paclitaxel upregulated proapoptotic and cell cycle arrest genes while downregulating ABCB1 gene and antiapoptotic genes. Thus, morin effectively reversed paclitaxel resistance in KBChR-8-5 drug-resistant cancer cells and concluded that morin resensitized the paclitaxel resistance in KBChR8-5 drug-resistant cancer cells.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Apoptose , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Flavonoides , Paclitaxel , Humanos , Flavonoides/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Paclitaxel/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Linhagem Celular Tumoral , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/química , FlavonasRESUMO
Flexible surface acoustic wave technology has garnered significant attention for wearable electronics and sensing applications. However, the mechanical strains induced by random deformation of these flexible SAWs during sensing often significantly alter the specific sensing signals, causing critical issues such as inconsistency of the sensing results on a curved/flexible surface. To address this challenge, we first developed high-performance AlScN piezoelectric film-based flexible SAW sensors, investigated their response characteristics both theoretically and experimentally under various bending strains and UV illumination conditions, and achieved a high UV sensitivity of 1.71 KHz/(mW/cm²). To ensure reliable and consistent UV detection and eliminate the interference of bending strain on SAW sensors, we proposed using key features within the response signals of a single flexible SAW device to establish a regression model based on machine learning algorithms for precise UV detection under dynamic strain disturbances, successfully decoupling the interference of bending strain from target UV detection. The results indicate that under strain interferences from 0 to 1160 µÎµ the model based on the extreme gradient boosting algorithm exhibits optimal UV prediction performance. As a demonstration for practical applications, flexible SAW sensors were adhered to four different locations on spacecraft model surfaces, including flat and three curved surfaces with radii of curvature of 14.5, 11.5, and 5.8 cm. These flexible SAW sensors demonstrated high reliability and consistency in terms of UV sensing performance under random bending conditions, with results consistent with those on a flat surface.
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Precise control of microparticle movement is crucial in high throughput processing for various applications in scalable manufacturing, such as particle monolayer assembly and 3D bio-printing. Current techniques using acoustic, electrical and optical methods offer precise manipulation advantages, but their scalability is restricted due to issues such as, high input powers and complex fabrication and operation processes. In this work, we introduce the concept of capillary wave tweezers, where mm-scale capillary wave fields are dynamically manipulated to control the position of microparticles in a liquid volume. Capillary waves are generated in an open liquid volume using low frequency vibrations (in the range of 10-100 Hz) to trap particles underneath the nodes of the capillary waves. By shifting the displacement nodes of the waves, the trapped particles are precisely displaced. Using analytical and numerical models, we identify conditions under which a stable control over particle motion is achieved. By showcasing the ability to dynamically control the movement of microparticles, our concept offers a simple and high throughput method to manipulate particles in open systems.
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To improve prediction performance and reduce artifacts in Raman spectra, we developed an eXtreme Gradient Boosting (XGBoost) preprocessing method to preprocess the Raman spectra of glucose, glycerol and ethanol mixtures. To ensure the robustness and reliability of the XGBoost preprocessing method, an X-LR model (which combined XGBoost preprocessing and a linear regression (LR) model) and a X-MLP model (which combined XGBoost preprocessing and a multilayer perceptron (MLP) model) were developed. These two models were used to quantitatively analyze the concentrations of glucose, glycerol and ethanol in the Raman spectra of mixed solutions. The proportion map of hyperparameters was firstly used to narrow down the search range of hyperparameters in the X-LR and the X-MLP models. Then the correlation coefficients (R2), root mean square of calibration (RMSEC), and root mean square error of prediction (RMSEP) were used to evaluate the models' performance. Experimental results indicated that the XGBoost preprocessing method achieved higher accuracy and generalization capability, with better performance than those of other preprocessing methods for both LR and MLP models.
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Photoacoustic spectroscopy (PAS) has been rapidly developed and applied to different detection scenarios. The acoustic pressure detection is an important part in the PAS system. In this paper, an ultrahigh sensitivity Fabry-Perot acoustic sensor with a T-shaped cantilever was proposed. To achieve the best acoustic pressure effect, the dimension of the cantilever structure was designed and optimized by finite element analysis using COMSOL Multiphysics. Simulation results showed that the sensitivity of such T-shaped cantilever was 1.5 times higher than that based on a rectangular cantilever, and the resonance frequency of T-shaped cantilever were able to modulate from 800â¯Hz to 1500â¯Hz by adjusting the multi-parameter characteristics. Experimental sensing results showed that the resonance frequency of T-shaped Fabry-Perot acoustic sensor was 1080â¯Hz, yielding a high sensitivity of 1.428 µm/Pa, with a signal-to-noise ratio (SNR) of 84.8â¯dB and a detectable pressure limit of 1.9 µPa/Hz1/2@1â¯kHz. We successfully used such acoustic sensor to measure acetylene (C2H2) concentration in the PAS. The sensitivity of PAS for C2H2 gas was 3.22â¯pm/ppm with a concentration range of 50â¯ppm â¼100â¯ppm, and the minimum detection limit was 24.91ppb.
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Excitation of multiple acoustic wave modes on a single chip is beneficial to implement diversified acoustofluidic functions. Conventional acoustic wave devices made of bulk LiNbO3 substrates generally generate few acoustic wave modes once the crystal-cut and electrode pattern are defined, limiting the realization of acoustofluidic diversity. In this paper, we demonstrated diversity of acoustofluidic behaviors using multiple modes of acoustic waves generated on piezoelectric-thin-film-coated aluminum sheets. Multiple acoustic wave modes were excited by varying the ratios between IDT pitch/wavelength and substrate thickness. Through systematic investigation of fluidic actuation behaviors and performances using these acoustic wave modes, we demonstrated fluidic actuation diversities using various acoustic wave modes and showed that the Rayleigh mode, pseudo-Rayleigh mode, and A0 mode of Lamb wave generally have better fluidic actuation performance than those of Sezawa mode and higher-order modes of Lamb wave, providing guidance for high-performance acoustofluidic actuation platform design. Additionally, we demonstrated diversified particle patterning functions, either on two sides of acoustic wave device or on a glass sheet by coupling acoustic waves into the glass using the gel. The pattern formation mechanisms were investigated through finite element simulations of acoustic pressure fields under different experimental configurations.
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Nanomechanical measurements, especially the detection of weak contact forces, play a vital role in many fields, such as material science, micromanipulation, and mechanobiology. However, it remains a challenging task to realize the measurement of ultraweak force levels as low as nanonewtons with a simple sensing configuration. In this work, an ultrasensitive all-fiber nanonewton force sensor structure based on a single-mode-tapered U-shape multimode-single-mode fiber probe is proposed and experimentally demonstrated with a limit of detection of ~5.4 nanonewtons. The use of the sensor is demonstrated by force measurement on a human hair sample to determine the spring constant of the hair. The results agree well with measurements using an atomic force microscope for the spring constant of the hair. Compared with other force sensors based on optical fiber in the literature, the proposed all-fiber force sensor provides a substantial advancement in the minimum detectable force possible, with the advantages of a simple configuration, ease of fabrication, and low cost.
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Transdermal drug delivery provides therapeutic benefits over enteric or injection delivery because its transdermal routes provide more consistent concentrations of drug and avoid issues of drugs affecting kidneys and liver functions. Many technologies have been evaluated to enhance drug delivery through the relatively impervious epidermal layer of the skin. However, precise delivery of large hydrophilic molecules is still a great challenge even though microneedles or other energized (such as electrical, thermal, or ultrasonic) patches have been used, which are often difficult to be integrated into small wearable devices. This study developed a flexible surface acoustic wave (SAW) patch platform to facilitate transdermal delivery of macromolecules with fluorescein isothiocyanates up to 2000 kDa. Two surrogates of human skin were used to evaluate SAW based energized devices, i.e., delivering dextran through agarose gels and across stratum corneum of pig skin into the epidermis. Results showed that the 2000 kDa fluorescent molecules have been delivered up to 1.1 mm in agarose gel, and the fluorescent molecules from 4 to 2000 kDa have been delivered up to 100 µm and 25 µm in porcine skin tissue, respectively. Mechanical agitation, localised streaming, and acousto-thermal effect generated on the skin surface were identified as the main mechanisms for promoting drug transdermal transportation, although micro/nanoscale acoustic cavitation induced by SAWs could also have its contribution. SAW enhanced transdermal drug delivery is dependent on the combined effects of wave frequency and intensity, duration of applied acoustic waves, temperature, and drug molecules molecular weights.
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Formation of bacterial films on structural surfaces often leads to severe contamination of medical devices, hospital equipment, implant materials, etc., and antimicrobial resistance of microorganisms has indeed become a global health issue. Therefore, effective therapies for controlling infectious and pathogenic bacteria are urgently needed. Being a promising active method for this purpose, surface acoustic waves (SAWs) have merits such as nanoscale earthquake-like vibration/agitation/radiation, acoustic streaming induced circulations, and localised acoustic heating effect in liquids. However, only a few studies have explored controlling bacterial growth and inactivation behaviour using SAWs. In this study, we proposed utilising piezoelectric thin film-based SAW devices on a silicon substrate for controlling bacterial growth and inactivation with and without using ZnO micro/nanostructures. Effects of SAW powers on bacterial growth for two types of bacteria, i.e., E. coli and S. aureus, were evaluated. Varied concentrations of ZnO tetrapods were also added into the bacterial culture to study their effects and the combined antimicrobial effects along with SAW agitation. Our results showed that when the SAW power was below a threshold (e.g., about 2.55 W in this study), the bacterial growth was apparently enhanced, whereas the further increase of SAW power to a high power caused inactivation of bacteria. Combination of thin film SAWs with ZnO tetrapods led to significantly decreased growth or inactivation for both E. coli and S. aureus, revealing their effectiveness for antimicrobial treatment. Mechanisms and effects of SAW interactions with bacterial solutions and ZnO tetrapods have been systematically discussed.
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Cytopathology, crucial in disease diagnosis, commonly uses microscopic slides to scrutinize cellular abnormalities. However, processing high volumes of samples often results in numerous negative diagnoses, consuming significant time and resources in healthcare. To address this challenge, a surface acoustic wave-enhanced multi-view acoustofluidic rotation cytometry (MARC) technique is developed for pre-cytopathological screening. MARC enhances cellular morphology analysis through comprehensive and multi-angle observations and amplifies subtle cell differences, particularly in the nuclear-to-cytoplasmic ratio, across various cell types and between cancerous and normal tissue cells. By prioritizing MARC-screened positive cases, this approach can potentially streamline traditional cytopathology, reducing the workload and resources spent on negative diagnoses. This significant advancement enhances overall diagnostic efficiency, offering a transformative vision for cytopathological screening.