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Evaluation of epithelial transport and oxidative stress protection of nanoengineered curcumin derivative-cyclodextrin formulation for ocular delivery
摘要： Ocular drug delivery has been a well-known route for the drug administration for the treatment of ocular diseases. However, numerous anatomical and physiological barriers prevailing in the eye itself create considerable challenges for achieving the necessitated therapeutic efficacy along with ocular bioavailability. However, recent advances in nanoengineered strategies hold definite promises in terms of devising improved ophthalmic medicines for the effective drug delivery to target the sites with enhanced ocular bioavailability. Curcumin, a hydrophobic polyphenol yellow colored compound, and its metabolic reduced product, tetrahydrocurcumin (THC), have been known for their beneficial pharmacological functions, such as anti-inflammatory or anti-oxidant activities at various tissue sites. However, the low aqueous solubility of these compounds results in their poor bioavailability, thereby limiting their widespread application. Therefore, in the present study, we investigated the changes in drug solubility by forming inclusion complexes with different derivatives of hydroxypropyl (HP)-cyclodextrins (CD). To this end, the spray drying technique was used for nanoengineering curcumin or THC-loaded formulations to improve the stability of formulations during the storage. The formulations were characterized in terms of physicochemical properties and cellular permeability. The results demonstrated that the encapsulation of curcumin (or THC) into the HP-CDs significantly increased the drug solubility and enhanced the corneal and retinal epithelial permeability. Curcumin or THC complexes in HP-CDs with improved bioavailability also induced anti-oxidant activity (SOD1, CAT1, and HMOX1) in higher levels in the ocular epithelial cells and showed oxidative protection effects in rabbit cornea tissues that will boost up their application in ocular medicine.
关键词： Ophthalmic formulation,Curcumin,Retinal pigmented epithelium,Cyclodextrins,Tetrahydrocurcumin,Cellular transport,Human corneal epithelium
更新于2025-11-21 11:24:58
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Screening of two-photon activated photodynamic therapy sensitizers using a 3D osteosarcoma model
摘要： Photodynamic therapy (PDT) involves a photosensitizing agent activated with light to induce cell death. Two-photon excited PDT (TPE-PDT) offers numerous benefits compared to traditional one-photon induced PDT, including an increased penetration depth and precision. However, the in vitro profiling and comparison of two-photon photosensitizers (PS) are still troublesome. Herein, we report the development of an in vitro screening platform of TPE-PS using a 3D osteosarcoma cell culture. The platform was tested using three different two-photon (2P) active compounds – a 2P sensitizer P2CK, a fluorescent dye Eosin Y, and a porphyrin derivative (TPP). Their 2P absorption cross-sections (σ2PA) were characterised using a fully automated z-scan setup. TPP exhibited a remarkably high σ2PA at 720 nm (8865 GM) and P2CK presented a high absorption at 850 nm (405 GM), while Eosin Y had the lowest 2P absorption at the studied wavelengths (<100 GM). The cellular uptake of PS visualized using confocal laser scanning microscopy showed that both TPP and P2CK were internalized by the cells, while Eosin Y stayed mainly in the surrounding media. The efficiency of the former two TPE-PS was quantified using the PrestoBlue metabolic assay, showing a significant reduction in cell viability after two-photon irradiation. The possibility of damage localization was demonstrated using a co-culture of adipose derived stem cells together with osteosarcoma spheroids showing no signs of damage to the surrounding healthy cells after TPE-PDT.
关键词： two-photon excited photodynamic therapy,PrestoBlue assay,photosensitizers,cellular uptake,localized damage,z-scan,3D osteosarcoma model
更新于2025-11-21 11:08:12
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Dual-action Platinum(II) Schiff Base Complexes: Photocytotoxicity and Cellular Imaging
摘要： Nine photo-stable Pt(II) Schiff base complexes [Pt(O^N^N^O)] (Pt1-Pt9) containing tetradentate salicylaldimine chelating ligands have been synthesized and characterized as potential photosensitisers for photodynamic therapy (PDT). The effects of electron-withdrawing versus electron-donating substituents on their electronic spectral properties are investigated. Pt1-Pt9 show broad absorption bands between 400-600 nm, which makes them useful for green-light photodynamic therapy. The complexes showed intense phosphorescence with emission maxima at ca. 625 nm. This emission was used to track their cellular localization in cancer cells. Confocal cellular imaging showed that the complexes localized mostly in the cytoplasm. In the dark, the complexes were non-toxic to A549 human lung cancer cells, but exhibited high photo-toxicity upon low-dose green light (520 nm, 7.02 J/cm2) irradiation via photo-induced singlet oxygen generation. Thus, these photoactive Pt(II) complexes have the potential to overcome the problem of drug resistance and side effects of current clinical Pt(II) drugs, and to act as both theranostic as well as therapeutic agents.
关键词： Schiff Base,Platinum(II),Photocytotoxicity,Cellular Imaging,Singlet oxygen
更新于2025-11-21 11:08:12
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Pharmacologic Alternatives to Riboflavin Photochemical Corneal Cross-Linking: A Comparison Study of Cell Toxicity Thresholds
摘要： PURPOSE. The efficacy of therapeutic cross-linking of the cornea using riboflavin photochemistry (commonly abbreviated as CXL) has caused its use to become widespread. Because there are known chemical agents that cross-link collagenous tissues, it may be possible to cross-link tissue pharmacologically. The present study was undertaken to compare the cell toxicity of such agents. METHODS. Nine topical cross-linking agents (five nitroalcohols, glyceraldehyde [GLYC], genipin [GP], paraformaldehyde [FA], and glutaraldehyde [GLUT]) were tested with four different cell lines (immortalized human corneal epithelial cells, human skin fibroblasts, primary bovine corneal endothelial cells, and immortalized human retinal pigment epithelial cells [ARPE-19]). The cells were grown in planar culture and exposed to each agent in a range of concentrations (0.001 mM to 10 mM) for 24 hours followed by a 48-hour recovery phase. Toxicity thresholds were determined by using the trypan blue exclusion method. RESULTS. A semiquantitative analysis using five categories of toxicity/fixation was carried out, based on plate attachment, uptake of trypan blue stain, and cellular fixation. The toxicity levels varied by a factor of 103 with the least toxic being mononitroalcohols and GLYC, intermediate toxicity for a nitrodiol and nitrotriol, and the most toxic being GLUT, FA, GP, and bronopol, a brominated nitrodiol. When comparing toxicity between different cell lines, the levels were generally in agreement. CONCLUSIONS. There are significant differences in cell toxicity among potential topical cross-linking compounds. The balance between cross-linking of tissue and cell toxicity should be borne in mind as compounds and strategies to improve mechanical tissue properties through therapeutic tissue cross-linking continue to develop.
关键词： protein cross-linking,cornea,cellular toxicity,keratoconus
更新于2025-09-23 15:23:52
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Design of a novel reversible structure for full adder/subtractor in quantum-dot cellular automata
摘要： Complementary Metal Oxide Semiconductor (CMOS) technology uses voltage levels for binary computation, whereas Quantum Dot-Cellular Automata (QCA) uses free electron location in the QCA cell for logic evaluation. This technology suggests very low power consumption, high speed and very dense structure for performing any logical circuit. Reversible logic is best mechanism with low power and high speed in circuit designing. Reversible gates have N input and N output lines that input lines mapped with output lines one by one. In this paper, a novel design of Reversible Full adder/subtractor with minimum number of cells has been proposed. QCADesigner software has been used to simulate the proposed design.
关键词： Quantum-dot Cellular Automata (QCA),Reversible Full adder/subtractor
更新于2025-09-23 15:23:52
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Lane-Level Localization and Mapping in GNSS-Challenged Environments by Fusing Lidar Data and Cellular Pseudoranges
摘要： A method for achieving lane-level localization in global navigation satellite system (GNSS)-challenged environments is presented. The proposed method uses the pseudoranges drawn from unknown ambient cellular towers as an exclusive aiding source for a vehicle-mounted light detection and ranging (lidar) sensor. The following scenario is considered. A vehicle aiding its lidar with GNSS signals enters an environment where these signals become unusable. The vehicle is equipped with a receiver capable of producing pseudoranges to unknown cellular towers in its environment. These pseudoranges are fused through an extended Kalman filter (EKF) to aid the lidar odometry, while estimating the vehicle’s own state (three-dimensional position and orientation) simultaneously with the position of the cellular towers and the difference between the receiver’s and cellular towers’ clock error states (bias and drift). The proposed method is computationally efficient and is demonstrated to achieve lane-level accuracy in different environments. Simulation and experimental results with the proposed method are presented illustrating a close match between the vehicle’s true trajectory and that estimated using the cellular-aided lidar odometry over a 1 km trajectory. A 60% reduction in localization error is obtained over the lidar odometry-only approach.
关键词： Lidar,Signals of opportunity,SLAM,Cellular
更新于2025-09-23 15:23:52
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Functional chlorin gold nanorods enable to treat breast cancer by photothermal/photodynamic therapy
摘要： Background: The existing chemo/radiotherapy fail to eliminate cancer cells due to the restriction of either drug resistance or radio tolerance. The predicament urges researchers to continuously explore alternative strategy for achieving a potent curative effect. Methods: Functional chlorin gold nanorods (Ce6-AuNR@SiO2-d-CPP) were fabricated aiming at treating breast cancer by photothermal/photodynamic therapy (PTT/PDT). The nanostructure was developed by synthesizing Au nanorods as the photothermal conversion material, and by coating the pegylated mesoporous SiO2 as the shell for entrapping photosensitizer Ce6 and for linking the D-type cell penetrating peptide (d-CPP). The function of Ce6-AuNR@SiO2-d-CPP was verified on human breast cancer MCF-7 cells and MCF-7 cells xenografts in nude mice. Results: Under combinational treatment of PTT and PDT, Ce6-AuNR@SiO2-d-CPP demonstrated a strong cytotoxicity and apoptosis inducing effects in breast cancer cells in vitro, and a robust treatment efficacy in breast cancer-bearing nude mice. The uptake mechanism involved the energy-consuming caveolin-mediated endocytosis, and Ce6-AuNR@SiO2-d-CPP in PTT/PDT mode could induce apoptosis by multiple pathways in breast cancer cells. Conclusion: Ce6-AuNR@SiO2-d-CPP demonstrated a robust efficacy in the treatment of breast cancer by photothermal/photodynamic therapy. Therefore, the present study could offer a new promising strategy to treat the refractory breast cancer.
关键词： PTT/PDT,apoptosis,cellular uptake,functional chlorin gold nanorods,cell penetrating peptide,cytotoxicity
更新于2025-09-23 15:23:52
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Simulation of grain evolution in solidification of silicon on meso-scopic scale
摘要： We present a cellular automata model for computing the grain evolution during directional solidification of silicon on a meso-scopic scale. Firstly, the method is applied to test cases with different shapes of the melt/crystal interface. In a second step we compute the case of an experiment with in-situ observation of the interface shape evolution (Tandjaoui et al., 2012). Here we also include the effect of twinning. The interchanging appearance of two twins could be revisited by our calculations. The probabilities used correspond to those which were analytically derived for an undercooling of 0.6 K (Lin and Lan, 2017). This undercooling is a typical value for a groove with facets (Miller and Popescu, 2017).
关键词： Directional solidification,Cellular automata,Multicrystalline silicon,Lattice Boltzmann methods
更新于2025-09-23 15:23:52
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Energy Harvesting Wireless Communications || Energy Harvesting in Next-Generation Cellular Networks
摘要： To handle the explosive growth of mobile traffic, next-generation cellular network will deploy more and more small-cell BSs (SBSs) in addition to the macro base stations (MBSs). The resultant network, namely, the heterogeneous network (HetNet), provides capacity boost on one hand but brings more energy consumption with the densely deployed SBSs on the other hand. In fact, due to the dynamics of wireless traffic load, many BSs are lightly loaded but almost work at their peak power, due to the elements like power amplifiers and supporting circuits. Unfortunately, these BSs can hardly be turned off for the coverage guarantee. To solve this problem, a new separation architecture called hyper-cellular network (HCN) is proposed, and the main idea is to decouple the function of control signaling from the function of data transmission, such that the data coverage can match the traffic dynamics in a more elastic way. Under HCN, SBSs are only utilized for high data rate transmission, whereas MBSs guarantee the network coverage and provide low data rate service. Therefore, SBSs can be turned off to save energy without worrying about the user coverage. To this end, its nature is to further power SBSs with renewable energy to save more grid power consumption. However, due to the randomness of renewable energy arrivals, it is challenging to manage wireless resource and the on-off states of energy harvesting (EH) BSs. It can be more challenging in HCN. First, diverse types of SBSs may be equipped with different kinds of energy sources, making the energy arrival statistically nonuniform over the space. In addition, the traffic load is nonevenly distributed across different base station (BS) tiers and also not in accordance with the energy arrivals over the spatial and temporal domains. To this end, on top of the techniques introduced in Chapter 4, in HCN the key to match the random energy arrival with the traffic load variation over time and space is to jointly optimize the working states of SBSs and the user traffic offloading. Although traffic offloading has been extensively studied in grid-powered cellular networks, the conventional offloading methods cannot be directly applied as they do not consider the energy states of BSs. Accordingly, energy-aware traffic offloading schemes are needed, and some energy-aware traffic offloading schemes have been proposed for single-tier homogeneous networks and two-tier HCN with one renewable energy-powered SBS, respectively. In the first part of the chapter, we will illustrate how to coordinate the on-off switching of SBSs with inter-tier traffic offloading, under the scenario with different types of SBSs, powered by various energy sources. The goal is to minimize the on-grid power consumption of the whole HCN system while satisfying the quality of service (QoS) requirements of users. Another emerging technology of next-generation cellular networks is to exploit edge caching with proactive services, like push. While the initial motivation of proactive caching and push is to reduce the duplicated content transmissions, and thus reduce the core network traffic load as well as the content delivery delay, it is also beneficial to address the mismatch between the energy and traffic in renewable energy-powered SBSs. Specifically, the contents can be cached at the storage of SBSs and then pushed to users earlier than the actual demands when there is sufficient harvested energy. The users can successfully get the contents when they actually require it even if at that time the SBS does not have enough energy for transmission. Consequently, the energy waste due to the battery overflow can be avoided as the harvested energy can be used effectively and timely. It can be viewed as transferring the harvested energy along with the timeline to the future to match the random energy arrival with the traffic needs. In the second part of this chapter, we will demonstrate the concept of integrating proactive service provisioning with EH HCN and provide a detailed study on the optimal policy design for content push from an EH-based SBS.
关键词： push,cellular networks,renewable energy,proactive caching,traffic offloading,quality of service,small-cell base stations,Markov decision process,Energy harvesting,hyper-cellular network
更新于2025-09-23 15:22:29
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[IEEE 2018 International Flexible Electronics Technology Conference (IFETC) - Ottawa, ON, Canada (2018.8.7-2018.8.9)] 2018 International Flexible Electronics Technology Conference (IFETC) - Comparative analysis of 1-bit memory cell in CMOS and QCA technology
摘要： Circuit designing with quantum dot cellular automata is one of the most recent technologies which aim at scaling of devices. In this logic design technique, the organization of quantum cells defines the circuit. It is based on field coupled computing. The quantum dot cellular automata has numerous advantages including less area occupied, lack of interconnects, higher clock frequency, and since it doesn't involve transfer of electrons or flow of current, it has the potential to perform low power calculation.This paper presents the comparison of 1-bit memory cell designed using CMOS technology and quantum dot cellular technology. The quantum dot cellular technology results in lesser occupied area at high clock frequency.
关键词： Static Random Access memory,Quantum dot cellular automata,eleven input majority gates
更新于2025-09-23 15:22:29