Search Results (19)

M2-like tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, particularly for cancer patients who are refractory to current immune checkpoint inhibitors (ICIs). Previously, we showed that prostaglandin E1 (PGE1) enhances the expression of M1 markers, including HLA-DR, on macrophages and induces the M1 polarization of TAMs in vivo. This study investigated the pharmacological mechanisms by which PGE1 and its derivatives suppress the expression of M2 markers, including TREM2 and CXCR2. Macrophages were cultured in ultralow attachment dishes either alone or in combination with liver cancer cell lines to generate homospheroids or heterospheroids. Cell surface marker expression was assessed by flow cytometry. Compared with homospheroids, M2 marker expression on macrophages in heterospheroids was significantly increased, suggesting that heterospheroid culture promotes M2 polarization. PGE1 decreased M2 marker expression in heterospheroids more effectively compared with PGE2, PGE3, misoprostol, and 13,14-dihydro-15-keto-PGE1, whereas the suppressive effects of 15-keto- and 13,14-dihydro-PGE1s, and lubiprostone were comparable to that of PGE1. Pharmacological inhibition of prostaglandin receptors revealed that EP2 and EP4 receptors are involved in the PGE1-induced reprogramming of M2-like macrophages to M1 macrophages. In summary, PGE1 and its derivatives are promising TAM-targeting immunotherapeutics. Full article

In recent years the global market of nanomedicine has experienced incredible growth owing to the advances in the field. This translation of the technique to the biomedical industry requires the development of production methods that deliver nanomedicines with a high degree of reproducibility between batches, combined with cost and time efficiency. The use of nanoparticles in medicine usually requires their surface functionalization to improve biocompatibility in addition to providing targeting capacities and/or stimuli-responsive behavior, among other interesting skills. Microfluidic technology has revolutionized the field both in nanomedicine synthesis and in preclinical evaluation. However, microfluidic-assisted synthetic procedures commonly require high-cost methods and equipment to fabricate the microreactors. The aim of this work is to present an ultra-low-cost microfluidic platform that permits the versatile modification of nanomaterials. To prove this approach, two different model nanoparticles with different natures: soft nanoparticles (liposomes) and rigid nanoparticles (mesoporous silica) have been decorated both with small molecules and with other nanoparticles, respectively, in order to evaluate the scope of this approach. The anchoring of the covalently attached elements has been performed using click chemistry, in compliance with the principles for further transfer to the drug industry. Full article

Two-dimensional cell culture systems lack the ability to replicate the complex, three-dimensional (3D) architecture and cellular microenvironments found in vivo. Multicellular spheroids (MCSs) present a promising alternative, with the ability to mimic native cell–cell and cell–matrix interactions and provide 3D architectures similar to in vivo conditions. These factors are critical for various biomedical applications, including cancer research, tissue engineering, and drug discovery and development. Polymeric materials such as hydrogels, solid scaffolds, and ultra-low attachment surfaces serve as versatile platforms for 3D cell culture, offering tailored biochemical and mechanical cues to support cellular organization. This review article focuses on the structure–property relationships of polymeric biomaterials that influence MCS formation, growth, and functionality. Specifically, we highlight their physicochemical properties and their influence on spheroid formation using key natural polymers, including collagen, hyaluronic acid, chitosan, and synthetic polymers like poly(lactic-co-glycolic acid) and poly(N-isopropylacrylamide) as examples. Despite recent advances, several challenges persist, including spheroid loss during media changes, limited viability or function in long-term cultures, and difficulties in scaling for high-throughput applications. Importantly, the development of MCS platforms also supports the 3R principle (Replacement, Reduction, and Refinement) by offering ethical and physiologically relevant alternatives to animal testing. This review emphasizes the need for innovative biomaterials and methodologies to overcome these limitations, ultimately advancing the utility of MCSs in biomedical research. Full article

Ciprofloxacin (CIP), a widely used broad-spectrum antibiotic, poses a serious threat to human health and environmental safety due to its residues. The complementary monomers molecularly imprinted electrochemiluminescence sensor (MIECLS) based on a polyvinylpyrrolidone-functionalized copper nanowires (CuNWs@PVP) luminescent probe was constructed for the ultra-sensitive detection of CIP. CuNWs with low cost and high conductivity exhibited near-infrared electrochemiluminescence (NIR ECL) properties, yet their self-aggregation and oxidation led to a weakened emission phenomenon. PVP with solvent affinity and large skeleton was in situ attached to CuNWs surface to avoid CuNWs sedimentation and aggregation, and self-enhanced ECL signals were achieved. The bifunctional monomers molecularly imprinted polymer (MIP) possessed complementary active centers that increased their affinity with CIP, enhancing the accurate and sensitive detection of the target substances. The linear range of CIP using MIECLS was 5.00 × 10⁻⁹–5.00 × 10⁻⁵ mol L⁻¹ with a low limit of detection (LOD) of 2.59 × 10⁻⁹ mol L⁻¹, while the recovery rates of CIP in the spiking recovery experiment were 84.39% to 92.48%. The combination of bifunctional monomer MIP and NIR copper-based nano-luminescent probe provides a new method for the detection of CIP in food. Full article

Research on endophytic fungi in desert plants, particularly the epiphytic or endophytic fungi of leaves, remains limited. In the extremely arid regions of northwest China, the ultra-xerophytic desert plant Haloxylon ammodendron harbors white fungi on its assimilating branches during autumn. The hyphae of these fungi intertwine, both internally and externally, comprising superficial, bridging, and endophytic types. The superficial hyphae attach to the surface of the assimilating branches and continuously grow and intersect, forming a thick layer of felt-like hyphae. This thick, felt-like layer of hyphae facilitates the adsorption of atmospheric water vapor on the surface of the hyphae or the assimilating branches, allowing H. ammodendron to capture atmospheric moisture, even under low humidity. Some superficial hyphae penetrate the cuticle into the epidermis, becoming bridging hyphae, which can rapidly transport water from the outside of the epidermis to the inside. The endophytic hyphae shuttle within the epidermis, achieving rapid water transfer within the epidermis of the assimilating branches. The presence of these three types of hyphae not only enables the assimilating branches of H. ammodendron to achieve rapid water absorption and transmission, but also facilitates the uptake of atmospheric water vapor under low humidity conditions. We discuss the mechanism by which the hyphae promote water absorption from the perspectives of hyphal composition, the formation of felt-like structures, and environmental conditions. We consider the presence of fungal hyphae on the surface of the H. ammodendron assimilating branches as an inevitable ecological process in arid environments. This study provides important theoretical insights into the mechanisms underlying the strong drought resistance of desert plants in extremely arid regions and offers strategies for desertification control. Full article

In vivo-matured oocytes exhibit higher developmental competence than those matured in vitro but mimicking the in vivo environment by in vitro conditions has been challenging. Until now, conventional two-dimensional (2D) systems have been used for in vitro maturation of bovine cumulus-oocytes-complexes (COCs). However, using such systems present certain limitations. Therefore, alternative low-cost methodologies may help to optimize oocyte in vitro maturation. Here, we used two different systems to culture COCs and evaluate their potential influence on embryo development and quality. In the first system, we used treated fumed silica particles to create a 3D microenvironment (liquid marbles; LM) to mature COCs. In the second system, we cultured COCs in 96-well plates with different dimensions (flat, ultra-low attachment round-bottom, and v-shaped 96-well plates). In both systems, the nuclear maturation rate remained similar to the control in 2D, showing that most oocytes reached metaphase II. However, the subsequent blastocyst rate remained lower in the liquid marble system compared with the 96-well plates and control 2D systems. Interestingly, a lower total cell number was found in the resulting embryos from both systems (LM and 96-well plates) compared with the control. In conclusion, oocytes matured in liquid marbles or 96-well plates showed no remarkable change in terms of meiotic resumption. None of the surface geometries influenced embryo development while oocyte maturation in liquid marbles led to reduced embryo development. These findings show that different geometry during maturation did not have a large impact on oocyte and embryo development. Lower embryo production after in vitro maturation in liquid marbles was probably detected because in vitro maturation was performed in serum-free medium, which makes oocytes more sensitive to possible toxic effects from the environment. Full article

In drilling and completion projects, sludge is formed as a byproduct when barite and oil are mixed, and later sticks to the casing. This phenomenon has caused a delay in drilling progress, and increased exploration and development costs. Since nano-emulsions have low interfacial surface tension, wetting, and reversal capabilities, this study used nano-emulsions with a particle size of about 14 nm to prepare a cleaning fluid system. This system enhances stability through the network structure in the fiber-reinforced system, and prepares a set of nano-cleaning fluids with adjustable density for ultra-deep wells. The effective viscosity of the nano-cleaning fluid reaches 11 mPa·s, and the system is stable for up to 8 h. In addition, this research independently developed an indoor evaluation instrument. Based on on-site parameters, the performance of the nano-cleaning fluid was evaluated from multiple angles by heating to 150 °C and pressurizing to 3.0 Mpa to simulate downhole temperature and pressure. The evaluation results show that the viscosity and shear value of the nano-cleaning fluid system is greatly affected by the fiber content, and the cleaning efficiency is greatly affected by the concentration of the nano-emulsion. Curve fitting shows that the average processing efficiency could reach 60–85% within 25 min and the cleaning efficiency has a linear relationship with time. The cleaning efficiency has a linear relationship with time, where R² = 0.98335. The nano-cleaning fluid enables the deconstruction and carrying of the sludge attached to the well wall, which accomplishes the purpose of downhole cleaning. Full article

Electrical Impedance Tomography (EIT) is a detection imaging technology developed 30 years ago. When the conventional EIT measurement system is used, the electrode and the excitation measurement terminal are connected with a long wire, which is easily affected by external interference, and the measurement result is unstable. In this paper, we developed a flexible electrode device based on flexible electronics technology, which can be softly attached to the skin surface for real-time physiological monitoring. The flexible equipment includes an excitation measuring circuit and electrode, which eliminates the adverse effects of connecting long wires and improves the effectiveness of measuring signals. At the same time, the design also uses flexible electronic technology to make the system structure achieve ultra-low modulus and high tensile strength so that the electronic equipment has soft mechanical properties. Experiments have shown that when the flexible electrode is deformed, its function is completely unaffected, the measurement results remain stable, and the static and fatigue performances are satisfactory. The flexible electrode has high system accuracy and good anti-interference. Full article

The conventional signal amplification strategies for surface plasmon resonance (SPR) biosensors involve the immobilization of receptors, the capture of target analytes and their recognition by signal reporters. Such strategies work at the expense of simplicity, rapidity and real-time measurement of SPR biosensors. Herein, we proposed a one-step, real-time method for the design of SPR biosensors by integrating magnetic preconcentration and separation. The target analytes were captured by the receptor-modified magnetic nanoparticles (MNPs), and then the biotinylated recognition elements were attached to the analyte-bound MNPs to form a sandwich structure. The sandwich hybrids were directly delivered to the neutravidin-modified SPR fluidic channel. The MNPs hybrids were captured by the chip through the neutravidin–biotin interaction, resulting in an enhanced SPR signal. Two SPR biosensors have been constructed for the detection of target DNA and beta-amyloid peptides with high sensitivity and selectivity. This work, integrating the advantages of one-step, real-time detection, multiple signal amplification and magnetic preconcentration, should be valuable for the detection of small molecules and ultra-low concentrations of analytes. Full article

The present studies were conducted to evaluate key serum proteins and other components that mediate anchorage-independent growth (3-D growth) of LNCaP prostate cancer cells as spheroids. The cells were cultured on ultra-low attachment plates in the absence and presence of fetuin-A and with or without extracellular vesicles. The data show that fetuin-A (alpha 2HS glycoprotein) is the serum protein that mediates 3-D growth in these cells. It does so by sequestering extracellular vesicles of various sizes on the surfaces of rounded cells that grow as spheroids. These vesicles in turn transmit growth signals such as the activation of AKT and MAP kinases in a pattern that differs from the activation of these key growth signaling pathways in adherent and spread cells growing in 2-D. In the process of orchestrating the movement and disposition of extracellular vesicles on these cells, fetuin-A is readily internalized in adhered and spread cells but remains on the surfaces of non-adherent cells. Taken together, our studies suggest the presence of distinct signaling domains or scaffolding platforms on the surfaces of prostate tumor cells growing in 3-D compared to 2-D. Full article

Several types of K⁺ channels play crucial roles in tumorigenicity, stemness, invasiveness, and drug resistance in cancer. Spheroid formation of human prostate cancer (PC) LNCaP cells with ultra-low attachment surface cultureware induced the up-regulation of cancer stem cell markers, such as NANOG, and decreased the protein degradation of the Ca²⁺-activated K⁺ channel K_Ca1.1 by down-regulating the E3 ubiquitin ligase, FBXW7, compared with LNCaP monolayers. Accordingly, K_Ca1.1 activator-induced hyperpolarizing responses were larger in isolated cells from LNCaP spheroids. The pharmacological inhibition of K_Ca1.1 overcame the resistance of LNCaP spheroids to antiandrogens and doxorubicin (DOX). The protein expression of androgen receptors (AR) was significantly decreased by LNCaP spheroid formation and reversed by K_Ca1.1 inhibition. The pharmacological and genetic inhibition of MDM2, which may be related to AR protein degradation in PC stem cells, revealed that MDM2 was responsible for the acquisition of antiandrogen resistance in LNCaP spheroids, which was overcome by K_Ca1.1 inhibition. Furthermore, a member of the multidrug resistance-associated protein subfamily of ABC transporters, MRP5 was responsible for the acquisition of DOX resistance in LNCaP spheroids, which was also overcome by K_Ca1.1 inhibition. Collectively, the present results suggest the potential of K_Ca1.1 in LNCaP spheroids, which mimic PC stem cells, as a therapeutic target for overcoming antiandrogen- and DOX-resistance in PC cells. Full article

Monitoring human health for early detection of disease conditions or health disorders is of major clinical importance for maintaining a healthy life. Sensors are small devices employed for qualitative and quantitative determination of various analytes by monitoring their properties using a certain transduction method. A “real-time” biosensor includes a biological recognition receptor (such as an antibody, enzyme, nucleic acid or whole cell) and a transducer to convert the biological binding event to a detectable signal, which is read out indicating both the presence and concentration of the analyte molecule. A wide range of specific analytes with biomedical significance at ultralow concentration can be sensitively detected. In nano(bio)sensors, nanoparticles (NPs) are incorporated into the (bio)sensor design by attachment to the suitably modified platforms. For this purpose, metal nanoparticles have many advantageous properties making them useful in the transducer component of the (bio)sensors. Gold, silver and platinum NPs have been the most popular ones, each form of these metallic NPs exhibiting special surface and interface features, which significantly improve the biocompatibility and transduction of the (bio)sensor compared to the same process in the absence of these NPs. This comprehensive review is focused on the main types of NPs used for electrochemical (bio)sensors design, especially screen-printed electrodes, with their specific medical application due to their improved analytical performances and miniaturized form. Other advantages such as supporting real-time decision and rapid manipulation are pointed out. A special attention is paid to carbon-based nanomaterials (especially carbon nanotubes and graphene), used by themselves or decorated with metal nanoparticles, with excellent features such as high surface area, excellent conductivity, effective catalytic properties and biocompatibility, which confer to these hybrid nanocomposites a wide biomedical applicability. Full article

Flotation in the mining industry is a very significant separation technique. It is known that fine and ultra-fine particles are difficult to float, leading to losses of valuable minerals, mainly due to their low collision efficiency with bubbles. Flotation of fine particles can be enhanced either by increasing the apparent particle size or by decreasing the bubble size. Literature review reveals that electroflotation resulted in higher recoveries of ultrafine particles as compared with dispersed-air flotation, because electrolytic bubbles are smaller in size. To this end, the best practical approach is to combine conventional air bubbles and micro-bubbles from water electrolysis. Therefore, the design, fabrication, and operation of a bench-scale micro-bubble generator through water electrolysis is proposed. Moreover, this electrolysis unit is adapted in a mechanical Denver-type flotation cell. The resulting hybrid flotation device is capable of producing bubbles within a wide range of diameters. The significance of this process is that micro-bubbles, attached tothe surface of fine particles, facilitate the attachment of conventional-sized bubbles and subsequently increase the flotation recovery of particles. Experimental flotation results so far on the hybrid device indicate the enhancement of fine particle recovery by approximately 10% with the addition of micro-bubbles. Full article

In this paper, an ultra-wideband flexible absorber is proposed. Based on a summary of the absorption mechanism, using lossless air to replace the heavy lossy dielectric layer will not substantially impact the absorption. The dielectric layer is only a thin layer of polyimide. The proposed absorber is a sandwich structure. The surface is a layer of copper metal ring and wire, and it is loaded with chip resistors to expand the absorber bandwidth. Simulated results show that the bandwidth of the proposed absorber, with an absorptivity of more than 90%, is 2.55–10.07 GHz, with a relative bandwidth over 119.2%. When the electromagnetic wave has a wide incident angle, the absorber still maintains a high absorption. This absorber has been fabricated by FPC (flexible printed circuit) technology. The proposed absorber was attached to the cylinder and measured. The measurement results are roughly the same as the simulation results. The fabricated absorber is easy to carry and flexible, such that it can easily be conformed to irregular objects. The proposed absorber is polarization-insensitive, low profile, thin, and portable, so it is easier to apply in a variety of practical fields. Full article

High-grade serous ovarian cancer (HGSOC) can originate in the fallopian tube and then spread to the ovary. Our objective was to evaluate the role of multicellular tumor spheroids (MTS) in ovarian metastasis. By testing a panel of murine oviductal epithelial (MOE) cells with genetic alterations mimicking those seen in HGSOC, we found that loss of PTEN allowed MTS formation under ultra-low adhesion conditions. Confirming these results in vivo, MTS-like structures were observed in the oviducts of PAX8^Cre/+ PTEN^flox/flox mice. MOE PTEN^shRNA cells could incorporate up to 25% wild type cells into MTS, while higher percentages of wild type cells resulted in a loss of MTS formation. MTS formation allowed MOE PTEN^shRNA cells to survive better under ultra-low adhesion conditions than control cells. MTS also attached to the ovarian stroma, as would be exposed during ovulation. Interestingly, MTS more robustly cleared monolayers of murine ovarian surface epithelia than murine ovarian fibroblasts. When xenografted into the ovarian bursa, OVCAR8 MTS were able to form tumors in the ovary at a similar rate as an equal number of OVCAR8 cells grown on traditional cell culture plastic. In conclusion, loss of a single gene (PTEN) allows the fallopian tube epithelia to form MTS, which survive better under ultra-low adhesion conditions, attach to the extracellular matrix exposed during ovulation, and colonize the ovary. These results suggest that MTS may contribute to seeding of the ovary in HGSOC patients. Full article