Next-generation 3D tumor modeling: A microfluidic platform with biocompatible red carbon dots for live cell imaging in co-cultured elongated spheroid tumor model.

Co-culture spheroids mimic tumor architecture more accurately than traditional 2D cell cultures, but non-invasive, long-term tracking of live cells within these 3D models remains a challenge. This study addresses this critical need by developing a novel approach for live cell imaging in U-87/HUF co-culture spheroids. We introduce water-soluble, biocompatible red carbon dots (R-CDs) exhibiting exceptional stability and brightness (21% quantum yield) specifically designed for imaging within these 3D models. Furthermore, we designed a microfluidic chip with ellipsoid-shaped microwells to efficiently generate two distinct co-culture spheroid types: direct mixing and core-shell. R-CDs enabled non-invasive tracking of U-87 cancer cell location within these 3D models demonstrating their efficacy for long-term monitoring of live cells in cancer research. This R-CD and microfluidic technology has the potential to accelerate cancer drug discovery by enabling live cell studies in 3D tumor models.

High-power 1018 nm Yb3+ doped fiber lasers with different YDF core and coiling diameters: theoretical and experimental study.

In this paper, the effect of the active fiber's core/cladding area ratio on the output parameters of 1018 nm fiber lasers has been investigated. In this regard, we conducted a comprehensive study of two fiber lasers that utilized 25/400 and 30/250 µm ytterbium-doped fibers (YDFs), both theoretically and experimentally. The optimum length of YDFs required for 40 dB of amplified spontaneous emission suppression was calculated. Theoretical studies also identified the YDF breaking zone for lengths greater than the optimum. The experimental results showed that selecting the proper dimensions and coiling diameter for the active fiber significantly increased the power and efficiency of the YDF laser. We obtained an output power of 943 W with a 75.5% slope efficiency for the co-pumped 30/250 µm YDFL which, to the best of our knowledge, is the highest reported value for the 1018 nm co-pumped fiber laser. An analysis of the experimental and theoretical results revealed that YDFs with a core/cladding area ratio greater than 1% are more suitable for realizing a high-power 1018 nm fiber laser. The findings of this study are crucial for the development of high-power 1018 nm fiber lasers with improved performance.

Chemical Compositions and Experimental and Computational Modeling of the Anticancer Effects of Cnidocyte Venoms of Jellyfish Cassiopea andromeda and Catostylus mosaicus on Human Adenocarcinoma A549 Cells.

Nowadays, major attention is being paid to curing different types of cancers and is focused on natural resources, including oceans and marine environments. Jellyfish are marine animals with the ability to utilize their venom in order to both feed and defend. Prior studies have displayed the anticancer capabilities of various jellyfish. Hence, we examined the anticancer features of the venom of Cassiopea andromeda and Catostylus mosaicus in an in vitro situation against the human pulmonary adenocarcinoma (A549) cancer cell line. The MTT assay demonstrated that both mentioned venoms have anti-tumoral ability in a dose-dependent manner. Western blot analysis proved that both venoms can increase some pro-apoptotic factors and reduce some anti-apoptotic molecules that lead to the inducing of apoptosis in A549 cells. GC/MS analysis demonstrated some compounds with biological effects, including anti-inflammatory, antioxidant and anti-cancer activities. Molecular docking and molecular dynamic showed the best position of each biologically active component on the different death receptors, which are involved in the process of apoptosis in A549 cells. Ultimately, this study has proven that both venoms of C. andromeda and C. mosaicus have the capability to suppress A549 cells in an in vitro condition and they might be utilized in order to design and develop brand new anticancer agents in the near future.

Closed-loop MOEMS accelerometer.

In this paper, a closed-loop micro-opto-electro-mechanical system (MOEMS) accelerometer based on the Fabry-Pérot (FP) interferometer is presented. The FP cavity is formed between the end of a cleaved single-mode optical fiber and the cross-section of a proof mass (PM) which is suspended by four U-shaped springs. The applied acceleration tends to move the PM in the opposite direction. The arrays of fixed and movable comb fingers produce an electrostatic force which keeps the PM in its resting position. The voltage that can provide this electrostatic force is considered as the output of the sensor. Using a closed-loop detection method it is possible to increase the measurement range without losing the resolution. The proposed sensor is fabricated on a silicon-on-insulator wafer using the bulk micromachining method. The results of the sensor characterization show that the accelerometer has a linear response in the range of ±5 g. In the closed-loop mode, the sensitivity and bias instability of the sensor are 1.16 V/g and 40 µg, respectively.

Method for tissue clearing: temporal tissue optical clearing.

Light absorption and scattering in biological tissue are significant variables in optical imaging technologies and regulating them enhances optical imaging quality. Optical clearing methods can decrease light scattering and improve optical imaging quality to some extent but owing to their limited efficacy and the potential influence of optical clearing agents on tissue functioning, complementing approaches must be investigated. In this paper, a new strategy of optical clearing proposed as time-dependent or temporal tissue optical clearing (TTOC) is described. The absorption and scattering in light interaction with tissue are regulated in the TTOC technique by altering the pulse width. Here, the dependence of optical properties of matter on the pulse width in a gelatin-based phantom was investigated experimentally. Then, a semi-classical model was introduced to computationally study of Ultra-short laser/matter interaction. After studying phantom, the absorption and scattering probabilities in the interaction of the pulse with modeled human skin tissue were investigated using the proposed model for pulse widths ranging from 1µs to 10fs. The propagation of the pulse through the skin tissue was simulated using the Monte Carlo technique by computing the pulse width-dependent optical properties (absorption coefficient µa, scattering coefficient µs, and anisotropy factor g). Finally, the penetration depth of light into the tissue and reflectance for different pulse widths was found.

Accuracy of peak-power compensation in fiber-guided and free-space acoustic-resolution photoacoustic microscopy.

Acoustic resolution photoacoustic microscopy (AR-PAM) has gained much attention in the past two decades due to its high contrast, scalable resolution, and relatively higher imaging depth. Multimode optical fibers (MMF) are extensively used to transfer light to AR-PAM imaging scan-head from the laser source. Typically, peak-power-compensation (PPC) is used to reduce the effect of pulse-to-pulse peak-power variation in generated photoacoustic (PA) signals. In MMF, the output intensity profile fluctuates due to the coherent nature of light and mode exchange caused by variations in the bending of the fibers during scanning. Therefore, using a photodiode (PD) to capture a portion of the total power of pulses as a measure of illuminated light on the sample may not be appropriate for accurate PPC. In this study, we have investigated the accuracy of PPC in fiber-guided and free-space AR-PAM systems. Experiments were conducted in the transparent and highly scattering medium. Based on obtained results for the MMF-based system, to apply PPC to the generated PA signals, tightly focused light confocal with the acoustic focus in a transparent medium must be used. In the clear medium and highly focused illumination, enhancement of about 45% was obtained in the homogeneity of an optically homogeneous sample image. In addition, it is shown that, as an alternative, free-space propagation of the laser pulses results in more accurate PPC in both transparent and highly scattering mediums. In free-space light transmission, enhancement of 25-75% was obtained in the homogeneity of the optically homogeneous sample image.

Investigation of anti-cancer effects of new pyrazino[1,2-a]benzimidazole derivatives on human glioblastoma cells through 2D in vitro model and 3D-printed microfluidic device.

AIMS: Recent studies show targeted therapy of new pyrazino[1,2-a]benzimidazole derivatives with COX-II inhibitory effects on different cancer cells. This study aimed to investigate 2D cell culture and 3D spheroid formation of glioblastoma multiforme (GBM) cells using a microfluidic device after exposure to these compounds. MAIN METHODS: After isolating astrocytes from human GBM samples, IC50 of 2,6-dimethyl pyrazino[1,2-a]benzimidazole (L1) and 3,4,5-trimethoxy pyrazino[1,2-a]benzimidazole (L2) were determined as 13 µM and 85 µM, respectively. Then, in all experiments, cells were exposed to subtoxic concentrations of L1 (6.5 µM) and L2 (42.5 µM), which were ½IC50. In the following, in two phases, cell cycle, migration, and gene expression through 2D cell culture and tumor spheroid formation ability using a 3D-printed microfluidic chip were assessed. KEY FINDINGS: The obtained results showed that both compounds have positive effects in reducing G2/M cell population and GBM cell migration. Furthermore, real-time gene expression data showed that L1 and L2 significantly impact the upregulation of P21 and P53 and down-regulation of cyclin D1, MMP2, and MMP9. On the other hand, GBM spheroids exposed to L1 and L2 become smaller with fewer live cells. SIGNIFICANCE: Our data on human isolated astrocyte cells in 2D and 3D cell culture conditions showed that L1 and L2 compounds could reduce GBM cells' invasion by controlling gene expressions associated with migration and proliferation. Moreover, designing microfluidic platform and related cell culture protocols facilitates the broad screening of 3D multicellular tumor spheroids derived from GBM tumor biopsies and provides effective drug development for brain gliomas.

Acute morphine administration, morphine dependence, and naloxone-induced withdrawal syndrome affect the resting-state functional connectivity and Local Field Potentials of the rat prefrontal cortex.

Opiates are among the widely abused substances worldwide. Also, the clinical use of opioids can cause unwanted and potentially severe consequences such as developing tolerance and dependence. This study simultaneously measured the changes induced after morphine dependence and naloxone-induced withdrawal syndrome on the resting-state functional connectivity (rsFC) and Local Field Potential (LFP) power in the prefrontal cortex of the rat. The obtained results revealed that acute morphine administration significantly increased the LFP power in all frequency bands, as well as the rsFC strength of the prefrontal cortex, and naloxone injection reversed this effect. In contrast, chronic morphine administration reduced neural activity and general correlation values in intrinsic signals, as well as the LFP power in all frequency bands. In morphine-dependent rats, after each morphine administration, the LFP power in all frequency bands and the rsFC strength of the prefrontal cortex were increased, and these effects were further enhanced after naloxone precipitated withdrawal syndrome. The present study concludes that general correlation merely reflects the field activity of the local cortices imaged.

Axial accuracy and signal enhancement in acoustic-resolution photoacoustic microscopy by laser jitter effect correction and pulse energy compensation.

In recent years, photoacoustic imaging has found vast applications in biomedical imaging. Photoacoustic imaging has high optical contrast and high ultrasound resolution allowing deep tissue non-invasive imaging beyond the optical diffusion limit. Q-switched lasers are extensively used in photoacoustic imaging due to the availability of high energy and short laser pulses, which are essential for high-resolution photoacoustic imaging. In most cases, this type of light source suffers from pulse peak-power energy variations and timing jitter noise, resulting in uncertainty in the output power and arrival time of the laser pulses. These problems cause intensity degradation and temporal displacement of generated photoacoustic signals which in turn deteriorate the quality of the acquired photoacoustic images. In this study, we used a high-speed data acquisition system in combination with a fast photodetector and a software-based approach to capture laser pulses precisely in order to reduce the effect of timing jitter and normalization of the photoacoustic signals based on pulse peak-powers simultaneously. In the experiments, maximum axial accuracy enhancement of 14 µm was achieved in maximum-amplitude projected images on XZ and YZ planes with ±13.5 ns laser timing jitter. Furthermore, photoacoustic signal enhancement of 77% was obtained for 75% laser pulses peak-power stability.

Three-Dimensional Imaging in Stem Cell-Based Researches.

Stem cells have an important role in regenerative therapies, developmental biology studies and drug screening. Basic and translational research in stem cell technology needs more detailed imaging techniques. The possibility of cell-based therapeutic strategies has been validated in the stem cell field over recent years, a more detailed characterization of the properties of stem cells is needed for connectomics of large assemblies and structural analyses of these cells. The aim of stem cell imaging is the characterization of differentiation state, cellular function, purity and cell location. Recent progress in stem cell imaging field has included ultrasound-based technique to study living stem cells and florescence microscopy-based technique to investigate stem cell three-dimensional (3D) structures. Here, we summarized the fundamental characteristics of stem cells via 3D imaging methods and also discussed the emerging literatures on 3D imaging in stem cell research and the applications of both classical 2D imaging techniques and 3D methods on stem cells biology.