Oxygen releasing patches based on carbohydrate polymer and protein hydrogels for diabetic wound healing: A review.

Diabetic wounds are among the major healthcare challenges, consuming billions of dollars of resources and resulting in high numbers of morbidity and mortality every year. Lack of sufficient oxygen supply is one of the most dominant causes of impaired healing in diabetic wounds. Numerous clinical and experimental studies have demonstrated positive outcomes as a result of delivering oxygen at the diabetic wound site, including enhanced angiogenesis, antibacterial and cell proliferation activities. However, prolonged and sustained delivery of oxygen to improve the wound healing process has remained a major challenge due to rapid release of oxygen from oxygen sources and limited penetration of oxygen into deep skin tissues. Hydrogels made from sugar-based polymers such as chitosan and hyaluronic acid, and proteins such as gelatin, collagen and hemoglobin have been widely used to deliver oxygen in a sustained delivery mode. This review presents an overview of the recent advances in oxygen releasing hydrogel based patches as a therapeutic modality to enhance diabetic wound healing. Various types of oxygen releasing wound healing patch have been discussed along with their fabrication method, release profile, cytocompatibility and in vivo results. We also briefly discuss the challenges and prospects related to the application of oxygen releasing biomaterials as wound healing therapeutics.

3D-printed bioresorbable poly(lactic-co-glycolic acid) and quantum-dot nanocomposites: Scaffolds for enhanced bone mineralization and inbuilt co-monitoring.

Multifunctional 3D-printed nanocomposites based on poly(lactic-co-glycolic acid), that is, PLGA (RESOMER® LG857S) were developed for simultaneous monitoring of cells and scaffold as a function of time and spectral responses. These were achieved by impregnating carbon quantum dots (CQDs) on PLGA using melt-blending, plasticating extrusion, and 3D-printing. The nanocomposites enabled enhanced bio-affinity and cellular interactions for bone tissue engineering (TE). PLGA (control) and PLGA-CQD scaffolds were used for growing human adipose-derived-stem-cells (ADSCs) and tested for cell biocompatibility, cellular adhesion, growth, and osteogenesis. CQDs were found to enhance the hydrophilicity of nanocomposites and promote cellular nesting. MTS assays confirmed that CQDs on PLGA act as cell anchoring sites, thereby enhancing seeding efficiency and cell proliferation. Alkaline phosphate tests showed increased osteogenesis and Alizarin assays confirmed enhanced bone mineralization on PLGA-CQD. The qPCR tests based on selected mRNA expressions showed that the incorporation of CQDs significantly enhanced osteogenesis of ADSCs during all three phases of cell differentiation. The intrinsic luminescence of the composites allowed label-free monitoring of cell proliferation and bone mineralization on the scaffolds. Thus, the CQDs facilitated significant enhancements in composite processability with customized fabrication of 3D printed scaffolds, bone tissue osteoconductivity, and monitoring of cell-scaffold activities, offering multifunctional benefits for bone TE.

Additive-Free All-Carbon Composite: A Two-Photon Material System for Nanopatterning of Fluorescent Sub-Wavelength Structures.

The major bottleneck in fabrication of engineered 3D nanostructures is the choice of materials. Adding functionality to these nanostructures is a daunting task. In order to mitigate these issues, we report a two-photon patternable all carbon material system which can be used to fabricate fluorescent 3D micro/nanostructures using two-photon lithography, with subwavelength resolution. The synthesized material system eliminates the need to use conventional two-photon absorbing materials such as two-photon dyes or two-photon initiators. We have used two different trifunctional acrylate monomers and carbon dots, synthesized hydrothermally from a polyphenolic precursor, to formulate a two-photon processable resin. Upon two-photon excitation, photogenerated electrons in the excited states of the carbon dots facilitate the free radical formation at the surface of the carbon dots. These radicals, upon interaction with vinyl moieties, enable cross-linking of acrylate monomers. Free-radical induced two-photon polymerization of acrylate monomers without any conventional proprietary two-photon absorbing materials was accomplished at an ultrafine subwavelength resolution of 250 nm using 800 nm laser excitation. The effect of critical parameters such as average laser power, carbon dot concentration, and radiation exposure were determined for the fabrication of one-, two-, and three-dimensional functional nanostructures, applicable in a range of domains where fluorescence and toxicity are of the utmost importance. A fabrication speed as high as 100 mm/s was achieved. The ability to fabricate functional 3D micro-/nanostructures is anticipated to instigate a paradigm shift in various areas such as metamaterials, energy storage, drug delivery, and optoelectronics to name a few.

Diagnostic and drug release systems based on microneedle arrays in breast cancer therapy.

Microneedle arrays have recently received much attention as cancer detection and treatment platforms, because invasive injections and detection of the biopsy are not needed, and drug metabolism by the liver, as well as adverse effects of systemic drug administration, are diminished. Microneedles have been used for diagnosis, vaccination, and in targeted drug delivery of breast cancer. In this review, we summarize the recent progress in diagnosis and targeted drug delivery for breast cancer treatment, using microneedle arrays to deliver active molecules through the skin. The results not only suggest that health and well-being of patients are improved, but also that microneedle arrays can deliver anticancer compounds in a relatively noninvasive manner, based on body weight, breast tumor size, and circulation time of the drug. Moreover, microneedles could allow simultaneous loading of multiple drugs and enable controlled release, thus effectively optimizing or preventing drug-drug interactions. This review is designed to encourage the use of microneedles for diagnosis and treatment of breast cancer, by describing general properties of microneedles, materials used for construction, mechanism of action, and principal benefits. Ongoing challenges and future perspectives for the application of microneedle array systems in breast cancer detection and treatment are highlighted.

Deep Q-Learning for Two-Hop Communications of Drone Base Stations.

In this paper, we address the application of the flying Drone Base Stations (DBS) in order to improve the network performance. Given the high degrees of freedom of a DBS, it can change its position and adapt its trajectory according to the users movements and the target environment. A two-hop communication model, between an end-user and a macrocell through a DBS, is studied in this work. We propose Q-learning and Deep Q-learning based solutions to optimize the drone's trajectory. Simulation results show that, by employing our proposed models, the drone can autonomously fly and adapts its mobility according to the users' movements. Additionally, the Deep Q-learning model outperforms the Q-learning model and can be applied in more complex environments.

3D bioprinting of engineered breast cancer constructs for personalized and targeted cancer therapy.

The bioprinting technique with specialized tissue production allows the study of biological, physiological, and behavioral changes of cancerous and non-cancerous tissues in response to pharmacological compounds in personalized medicine. To this end, to evaluate the efficacy of anticancer drugs before entering the clinical setting, tissue engineered 3D scaffolds containing breast cancer and derived from the especially patient, similar to the original tissue architecture, can potentially be used. Despite recent advances in the manufacturing of 3D bioprinted breast cancer tissue (BCT), many studies still suffer from reproducibility primarily because of the uncertainty of the materials used in the scaffolds and lack of printing methods. In this review, we present an overview of the breast cancer environment to optimize personalized treatment by examining and identifying the physiological and biological factors that mimic BCT. We also surveyed the materials and techniques related to 3D bioprinting, i.e, 3D bioprinting systems, current strategies for fabrication of 3D bioprinting tissues, cell adhesion and migration in 3D bioprinted BCT, and 3D bioprinted breast cancer metastasis models. Finally, we emphasized on the prospective future applications of 3D bioprinted cancer models for rapid and accurate drug screening in breast cancer.

Two-photon active nucleus-targeting carbon dots: enhanced ROS generation and photodynamic therapy for oral cancer.

Novel conjugated carbon dots (CDs) were synthesized as two-photon active photosensitisers to unleash lethal reactive oxygen species (ROS) for nucleus-targeting photodynamic therapy (PDT). To enhance the therapeutic efficiency and preclude non-specific CD uptake, we employed a combination of folic acid and curcumin for two-photon NIR-triggered ROS generation and enhanced internalization in the nucleus. Consequently, enhanced destruction of cancer cells occurred by directly attacking the DNA. The intrinsic ROS generation and nucleus-targeting ability of CDs introduced multifunctional two-photon active nanoprobes within a single platform for enhanced PDT in oral cancer theranostics.

A Cooperative Machine Learning Approach for Pedestrian Navigation in Indoor IoT.

This paper presents a system based on pedestrian dead reckoning (PDR) for localization of networked mobile users, which relies only on sensors embedded in the devices and device- to-device connectivity. The user trajectory is reconstructed by measuring step by step the user displacements. Though step length can be estimated rather accurately, heading evaluation is extremely problematic in indoor environments. Magnetometer is typically used, however measurements are strongly perturbed. To improve the location accuracy, this paper proposes a novel cooperative system to estimate the direction of motion based on a machine learning approach for perturbation detection and filtering, combined with a consensus algorithm for performance augmentation by cooperative data fusion at multiple devices. A first algorithm filters out perturbed magnetometer measurements based on a-priori information on the Earth's magnetic field. A second algorithm aggregates groups of users walking in the same direction, while a third one combines the measurements of the aggregated users in a distributed way to extract a more accurate heading estimate. To the best of our knowledge, this is the first approach that combines machine learning with consensus algorithms for cooperative PDR. Compared to other methods in the literature, the method has the advantage of being infrastructure-free, fully distributed and robust to sensor failures thanks to the pre-filtering of perturbed measurements. Extensive indoor experiments show that the heading error is highly reduced by the proposed approach thus leading to noticeable enhancements in localization performance.

Two-Photon Active Boron Nitride Quantum Dots for Multiplexed Imaging, Intracellular Ferric Ion Biosensing, and pH Tracking in Living Cells.

Nanoparticles are key vehicles for targeted therapies because they can pass through biological barriers, enter into cells, and distribute within cell structures. We investigated the synthesis of blue and green emissive hexagonal boron nitride quantum dots (hBNQDs) using a liquid-exfoliation technique followed by hydrothermal treatment. A distinct shift from blue to bright-green emission was observed upon surface passivating the dots using poly(ethylene glycol) or PEG200 under the same UV irradiation. The quantum yield of the hBNQDs increased with the surface passivation. Multiplexed imaging was accomplished using the hBNQDs in conjunction with organic dyes. The hBNQDs provided images with distinctive emission wavelengths and fluorescence lifetimes. Although the fluorescence signals of blue- and green-emissive hBNQDs overlap spectrally with those of the emission wavelengths of the organic dyes, the fluorescence lifetime data were resolved temporally using software-based time gates. The blue-emissive hBNQD-b quantum dots were validated as sensitive platforms for detecting intracellular ferric ions with a low limit of detection (20.6 nM). The green-emissive hBNQD-g quantum dots successfully identified intracellular variations in pH, and the localization in human breast cancer cells was determined during their life cycles via fluorescence lifetime imaging.

Inhibition of Notch signaling pathway using γ-secretase inhibitor delivered by a low dose of Triton-X100 in cultured oral cancer cells.

How to effectively delivering therapeutic agents, including γ-secretase inhibitors (GSIs), into live cells, remains a significant challenge. This study assessed the effect of Notch signaling inhibition by examining levels of the Notch1 intracellular domain (N1ICD) in cultured oral cancer cells analyzed with random stitched images (2D) and 3D visualizations using confocal microscopy and quantitative gene analysis. Substantially, we have developed a novel method to assist the delivery of γ-secretase inhibitor, DAPT, into live cells in the presence of an effective minimum concentration of Triton-X100 (0.001%) without damaging cell activity and membrane integrity assessed with cell proliferation assays. The images obtained in this study showed that DAPT alone could not block the γ-secretase inhibitor despite inhibiting cell growth. Further analysis of quantitative gene expressions of Notch signaling canonical pathway to verify the effectiveness of the novel method for delivering inhibitor into live cells, displayed deregulation of Notch1, Delta-like ligand 1 (DLL1) and hairy and enhancer of split 1 (Hes1). Our data suggest that Notch1/Hes1 signaling pathway is deactivated using DAPT with a low dose of Triton-X100 in this cancer cells. And the finding also suggests that Notch1 could be engaged by DLL1 to promote differentiation in oral cancer cells. Using this approach, we demonstrate that Triton-X100 is a promising and effective permeabilization agent to deliver γ-secretase inhibitor DAPT into live oral epithelial cells. This strategy has the potential to implicate in the treatment of cancer diseases.

Co-Doping of Activated Graphene for Synergistically Enhanced Electrocatalytic Oxygen Reduction Reaction.

Doping of graphene has emerged as a key strategy to improve the electrocatalytic performance of the oxygen reduction reaction (ORR). Activated graphene co-doped with iodine and nitrogen atoms (NIG) was developed in this work using a facile scalable approach. The onset potential, current density, and four-electron reduction pathway of the newly developed catalyst were significantly improved. The charge-transfer resistance of co-doped NIG was found to be much lower than nitrogen-doped graphene (NG); furthermore, the stability of NIG and its resistance to methanol crossover were also improved. The synergistically enhanced ORR performance of NIG was found to be a result of a high strain and size advantage of the larger iodine atom clusters (compared to nitrogen), which facilitate the simultaneous enrichment of anode electrons and O2 and H2 O molecule transport at catalytic sites, inducing four-electron transfer in a single step. These results are promising for application in alkaline fuel cells.

Edge-enriched graphene quantum dots for enhanced photo-luminescence and supercapacitance.

Graphene quantum dots (GQDs) with their edge-bound nanometer-size present distinctive properties owing to quantum confinement and edge effects. We report a facile ultrasonic approach with chemical activation using KOH to prepare activated GQDs or aGQDs enriched with both free and bound edges. Compared to GQDs, the aGQDs we synthesized had enhanced BET surface area by a factor of about six, the photoluminescence intensity by about four and half times and electro-capacitance by a factor of about two. Unlike their non-activated counterparts, the aGQDs having enhanced edge states emit enhanced intense blue luminescence and exhibit electrochemical double layer capacitance greater than that of graphene, activated or not. Apart from their use as part of electrodes in a supercapacitor, the superior luminescence of aGQDs holds potential for use in biomedical imaging and related optoelectronic applications.

Introducing single dose liposomal amphotericin B for the treatment of visceral leishmaniasis in rural bangladesh: feasibility and acceptance to patients and health staff.

Background. For the treatment of visceral leishmaniasis in Bangladesh, single dose liposomal amphotericin B (ambisome) is supposed to be the safest and most effective treatment. Specific needs for application and storage raise questions about feasibility of its implementation and acceptance by patients and health staff. Methods. The study was carried out in the most endemic district of Bangladesh. Study population includes patients treated with ambisome or miltefosine, hospital staff, and a director of the national visceral leishmaniasis program. Study methods include direct observation (subdistrict hospitals), open interviews (heath staff and program personnel), structured questionnaires, and focus group discussions (patients). Results. Politicalcommitment for ambisome is strong; the general hospital infrastructure favours implementation but further strengthening is required, particularly for drug storage below 25°C (refrigerators), back-up energy (fuel for generators), and supplies for ambisome administration (like 5% dextrose solution). Ambisome created high satisfaction in patients and hospital staff, less adverse events, and less income loss for patients compared to miltefosine. Conclusions. High political commitment, general capacities of subdistrict hospitals, and high acceptability favour the implementation of ambisome treatment in Bangladesh. However, strengthening of the infrastructure and uninterrupted supplies of essential accessories is mandatory before introducing sLAB in Bangladesh.

High-yield aqueous phase exfoliation of graphene for facile nanocomposite synthesis via emulsion polymerization.

Aqueous phase exfoliation was developed for producing high-yield graphene nanosheets from expanded graphite (EG). The process included ultrasonication with sodium dodecyl sulfate (SDS) emulsion in aqueous phase. The high throughput exfoliation process was characterized by UV-vis spectroscopy, transmission electron microscopy (TEM) and electrical impedance spectroscopy (EIS). Controlled sonication experiments revealed that optimum exfoliation corresponds to maxima in UV-vis spectra. TEM results showed that the exfoliated graphene comprised nanoflakes having ≤5 layers (~60%) and ≤10 layers for 90% of the product. The potential use of this highly dispersed graphene was demonstrated by one-pot synthesis of graphene/polymer composite via in situ emulsion polymerization with styrene. The integrated role of SDS included adsorption and exfoliation of graphite, dispersion of graphene produced and assisting with micelle formation in emulsion. The high surface area graphene nanosheets as dispersed phase in polymeric nanocomposites showed significant improvement in thermal stability and electrical conductivity.