The COVID-19 crisis has brought unprecedented strain on healthcare systems around the world. It has perhaps taught us some key lessons that are worth considering and addressing to help build more sustainable health systems as well as improve our ability to combat future epidemics.

Regeneration is a fundamental perpetual tissue process much attributed to functions of adult stem cell. In last decades delivery of adult stem cells to restore tissue structure is widely adopted in regenerative medicine. However, delivery of stem cells can not complete the task of human body regeneration effectively as far as cells need a basis to form a tissue. Certain improvement can be achieved when cells are organized to cells sheets (CS) – primitive tissue-engineered structures comprising of viable cells and ECM proteins. This led us to an assumption that after damage an intermediate feeder is structure formed as a ground for future tissue resulting in gradients of stimuli required to attract other cells (vascular, neural, epithelial, parenchyma etc.) in an organized manner. This feeder acquires increasing heterogeneity and becomes a guiding feeder that provides basic level of organization to increase complexity of structure up to normal tissue. We also highlight potential role of adult mesenchymal stromal cells (MSC) as the main source of guiding feeder and support it by our recent knowledge of their biological function. Finally, we assume that CS known to be a feasible delivery tool in therapeutics resemble guiding feeder and show our own data indicating properties of MSC-based CS. Furthermore, this concept shifts our understanding of therapeutic mechanism underlying a widely known delivery method for regenerative medicine.

The impact of the agriculture net carbon effect is crucial for climate change mitigation, yet research on this topic in China is currently insufficient. In this study, the carbon balance ratio (CBR) is used to characterise the net carbon effect of agriculture, and the spatial Durbin model and threshold regression model were used to empirically analyse the CBR with a sample of 30 provincial-level regions in China from 2004 to 2019. The aim was to investigate the mechanism of the influence of the land management scale (SCALE) of farming on the CBR. The results of the study indicate that national farming generally has a net sink effect, with large changes in interannual fluctuations; the expansion of SCALE has an obvious role in increasing sinks and reducing emissions, and has a positive spatial spillover effect on CBR, with significant spatial heterogeneity. Furthermore, as the SCALE expands, the direction of the influence of rural residents’ income and education level on CBR changes in the opposite direction, showing a significant non-linear relationship characteristic. However, in most areas, the SCALE threshold has not yet been reached, suggesting that the improvement in education levels can still offset the negative impact of economic income growth in the short term. The study recommends paying attention to the role of farmers’ human capital, changing production methods, and implementing carbon peaking and carbon neutrality goals to enhance the net sink effect of the farming industry, which would be achieved by increasing land management scale.

Optical beam splitter is used for dividing an input optical beam into several separate beams with specific power ratio. Usually, conventional beam splitters have bulky dimensions and fixed dividing ratio which significantly limit the design of new miniaturized optical devices and integrated optical circuits. We propose and investigate a novel physical concept of a miniaturized planar optical splitter/coupler with a switching element in the form of a photonic molecule (PM) pair dispersing input optical fluxes along multiple ways with variable power proportions. The structural design of the proposed splitter is based on a silicon-on-insulator (SOI) platform and composed of high-quality resonators in the form of electromagnetically coupled submicron-sized microcylinders. The control on the power division ratio and the selection of optical beam directions is realized by tuning the photonic splitter structure to the corresponding resonance of PM supermode. Compared to known analogues, the proposed design is easy to fabricate, suitable for integration into a "System-on-a-chip" platform and can dynamically change the beam power division ratio by input wave-phase manipulation.

The initiation of micro-cracks in concrete is primarily due to its brittleness, which causes severe impacts on the overall behavior of the concrete. However, incorporating fibers in concrete could significantly improve its mechanical properties. The current study demonstrates the influence of two types of fibers on the mechanical properties of concrete. Nylon Fiber Threads (NFT) and Nylon Fiber Strands (NFS) at a fiber content of 2.5 kg/m³ were incorporated in the concrete mix. Concrete with a compressive strength of 30 MPa and a water-cement ratio of 0.4 was produced to investigate the fresh and mechanical properties of conventional and nylon-fiber reinforced concrete (NFRC). The concrete prims and cylinders were tested for compressive, splitting, and flexural strength using ASTM standards (ASTM C-39, C-496, and D-790, respectively). It was found that NFT-reinforced samples achieved higher mechanical properties of concrete (13.05%) compared to NFS-reinforced samples. Test results showed that incorporation of nylon fibers (NF) in concrete decreased the compressive strength of cylindrical and cubical specimens by 0–10% and 5–15%, respectively. However, it increased the splitting tensile and flexural strengths by 0-15%, and 5-15% respectively. Furthermore, the incorporation of NF in concrete significantly improved the ductility and delayed the crack initiation in concrete.

A new approach to the measurement with elastic lidar of depolarization produced by atmospheric aerosols is presented. The system uses two different telescopes: one for depolarization measurements and another for total-power measurements. The system architecture and principle of operation are described. The first experimental results are also presented, corresponding to a collection of atmospheric conditions over the city of Barcelona.

Adeno-associated viruses (AAVs) have been used for liver gene therapy. Hemgenix and Roctavian are AAV-based treatments for hemophilia B and A, respectively. They cost $3 million and $2.8 million per dose, respectively. While AAV vectors may eventually be cheaper to mass produce, a bacteria-based DNA delivery system might be much cheaper for patients. Also, “bactofection” would allow for the delivery of much larger DNA packages. Such a bacterial system may now be possible, and a prototype for the liver could possibly be developed immediately.

The release of the active substance from the matrix modified-release tablets based on Kollidon®SR and chitosan depends on its solubility in the dissolution medium and on the composition of the matrix-forming polymers. The study is based on new oral matrix tablets based on Kollidon®SR and chitosan, formulated to optimize the low oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug, a class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method, and their combination at 1:1, 1:2, 1:3 chlorzoxazone/ excipients, 20%-40% (w/w) Kollidon®SR, 3-7% (w/w) chitosan and the auxiliary substances were formulated in constant concentrations. Pharmaco-technical characterization included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, Carr Index), and of pharmaco-chemical characteristics (mass and dose uniformity, thickness, diameter, mechanical strength, Friability, degree of softening, in vitro release profile) of the tablets. Based on the initial evaluation of the pharmaco-technical analysis, pharmaco-chemical characteristics, and in vitro release profile, only three matrix tablet formulations (F1b, F2b, and F3b) were further tested. They were evaluated through Fourier-transform infrared spectrometry, X-ray Diffraction, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified release oral formulations. In vitro kinetic study reveals a complex mechanism of release occurring in the first (0 - 2 hours) and second (2.0 hours – 36 hours) steps of drug release. Two factors have been calculated to assess the release profile of chlorzoxazone: f1 - the similarity factor and f2 - the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. In vitro dissolution tests revealed the F2b sample, data suggesting a faster drug release. The three formulations showed optimum pharmaco-technical properties and in vitro kinetic study, and they had tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone.

European cities are motivated to act towards the achievement of climate-neutral mobility solutions. Often, though, they are facing many challenges when bringing (innovative) sustainable mobility solutions forward. Capacity building that fills skills gap and/or enables acquisition of new ones related to the planning and implementation of such solutions can empower local/ regional authorities to identify them, adopt them and eventually deliver them properly. The aim of this paper is to present the Key Performance Indicator (KPI) framework that has been used for the assessment of the effectiveness of the Learning and Exchange Programme applied in an EU-funded project. It presents the methodological steps for the adoption of the KPIs, as well as the tools used for the selection of the KPI data and the KPI monitoring at project level. It also presents the results from the application of the framework for assessing the knowledge performance towards the deployment of sustainable mobility solutions. It finally reflects on recommendations for applying the KPI framework to other cases and thematic contents.

The use of sensors in monitoring of lateral accelerations in delivery van transport focuses on measuring lateral accelerations on routes with roundabouts and curves to increase road safety. Using microelectromechanical system (MEMS) sensors, it measures the lateral accelerations acting on the vehicle and the load being transported during the test drives to study vehicle dynamics for cargo securing. Using an accelerometer and position tracking, accelerations can be detected when traversing curves and roundabouts at selected locations on the vehicle. The level of accelerations on the roof of the vehicle was found to be like those occurring on a lashed load with limited movements, where regression analysis can be used to determine the relationship between lateral accelerations at different sensor positions. If we compare the mean values of the lateral accelerations of the individual events between the sensors, the sensor on the side of the vehicle body at the height of the sensor on the load had approximately 5% lower mean values than the sensor on the roof. The sensor on the load measured approximately 5% higher mean values than the sensor on the roof. Hence, the mean lateral accelerations of the individual events for the sensor on the load are 10% higher than for the sensor at the same height on the vehicle body. From the above testing, we can say that the values of the mean lateral accelerations of the van from the sensor on the roof of the vehicle, are closer to the values of the accelerations of the sensor on the load than to the values of the sensor on the body of the vehicle at the same height.

Biomimetic delivery systems (BDSs), inspired by the intricate designs of biological systems, have emerged as a groundbreaking paradigm in nanomedicine, offering unparalleled advantages in therapeutic delivery. These systems, encompassing platforms such as liposomes, protein-based nanoparticles, extracellular vesicles, and polysaccharides, are lauded for their targeted delivery, minimized side effects, and enhanced therapeutic outcomes. However, the translation of BDSs from research settings to clinical applications is fraught with challenges, including reproducibility concerns, physiological stability, and rigorous efficacy and safety evaluations. Furthermore, the innovative nature of BDSs demands a reevaluation and evolution of existing regulatory and ethical frameworks. This review provides an overview of BDSs, delve into the multifaceted translational challenges and present emerging solutions, underscored by real-world case studies. Emphasizing the potential of BDSs to redefine healthcare, we advocate for sustained interdisciplinary collaboration and research. As our understanding of biological systems deepens, the future of BDSs in clinical translation appears promising, with a focus on personalized medicine and refined patient-specific delivery systems.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

The prevalence of chronic diseases is dramatically increasing demand for emergency healthcare. Existing systems rely on patients self-identifying symptoms, causing dangerous delays. This study develops an AI and IoT-powered “digital twin” solution to enable continuous real-time monitoring and timely prediction of diverse medical emergencies. A digital twin is a virtual representation of an individual, modeled using multidimensional physiological data from wearable sensors. Machine learning techniques analyze patterns in this data to identify anomalies and predict emergencies like heart attacks or falls. A key contribution is an optimized ensemble algorithm combining gradient boosted trees, neural networks, and other techniques to accurately detect emergency events. Evaluation on a dataset of 9158 samples shows the digital twin identifies key emergencies with over 90% recall, enabling prevention and rapid response. It allows risk stratification and personalized interventions based on early warnings, circumventing over 2 million avoidable emergency room visits annually. This study demonstrates the feasibility of an integrated, predictive, patient-centric emergency response system enabled by digital twin technology.

Skin cancer is a disease that reflects most malignant neoplasms worldwide, whose rate of involvement has increased significantly in recent decades. Treatments that offer efficient results with attenuation of adverse reactions and greater patient compliance have been the subject of many systematic investigations. This review aims to qualitatively present published works that showed new strategies to increase the penetration power of natural substances through the skin in the topical treatment against skin cancer. In this sense, nanoengineering mechanisms, the iontophoresis technique, and photodynamic therapy using natural products (NP) contribute to new knowledge about substance carrier strategies in topical treatments against skin cancer.

Our concern was to obtain a biocomposite material with improved properties of the constituent materials (poly(lactic- co-glycolic acid) (PLGA) and zinc–boron (Zn–B) complex) in accordance with the novelties in the field of delivery systems for therapeutic agents which lately redefine the importance of biopolymer nanocomposites with PLGA (biodegradable composites). The advantages of such a biomaterial target the health system, being easy to obtain, through a cost-effective method. The water/oil/water double emulsion method also allows the adjustment of the synthesis parameters, to maximize the degree of Zn–B complex encapsulation. The morphological aspects of the samples (size, shape, porosity) were established by scanning electron microscopy (SEM). Particle size distribution (by volume and by number) was determined by direct light scattering (DLS). For all the synthesized materials, the observed morphology was typical for PLGA, spherical one. The particle size distribution showed that depending on the synthesis conditions, the particles can be obtained with diameters between 10–450 nm range and the value of the zeta potential (ZP) shows that the particles have electronegative surface charge, which offers a favorable perspective on the phenomena of aggregation, flocculation, dispersion. It was observed, applying the design of experiments (DoE), that the size of the particles increased with increasing amounts of PLGA and polyvinyl alcohol (PVA) in the formulation, while ZP increased with higher PLGA and smaller PVA. The encapsulation efficiency was determined by ultra-high performance liquid chromatography/mass spectrometry (UHPLC/MS).

Hydrogels (gels) are attractive tools for tissue engineering and regenerative medicine due to their potential for drug delivery and ECM-like composition. In this study, we use rheology to characterize GelMA/alginate gels loaded with human platelet lysate (PL). We then characterize these gels from a physicochemical perspective and evaluate their ability to transport PL proteins, their pore size, and their rate of degradation. Finally, their biocompatibility is evaluated. We describe how alginate changes the mechanical behavior of the gels from elastic to viscoelastic after ionic (calcium-mediated) crosslinking. In addition, we positively report the release of PL proteins and relate it to the degradation profile of the gels and the biocompatibility of the gels. Thus, the developed gels represent attractive substrates for both cell studies and bioactive materials.

Sustainable supply chains have become increasingly crucial to address environmental and social challenges faced by societies worldwide. Last-mile delivery, which involves delivering products from a distribution center or warehouse to the final destination, typically a consumer's doorstep, is an essential component of the supply chain. However, it faces numerous challenges such as traffic congestion, air and noise pollution, and carbon emissions. This research paper explores the viability of last-mile delivery solutions for sustainable supply chains. The study reviews the literature on last-mile delivery challenges, sustainable last-mile delivery solutions, and case studies of sustainable last-mile delivery solutions. The results indicate that innovative last-mile delivery solutions, such as electric vehicles, cargo bikes, and drones, have the potential to reduce environmental impact and improve the efficiency of last-mile delivery while enhancing social equity. Additionally, partnerships between different stakeholders, including governments, logistics companies, and consumers, can contribute to the development of sustainable last-mile delivery solutions. The study concludes that sustainable last-mile delivery solutions are essential to achieving sustainable supply chains and recommends further research to explore the economic feasibility and scalability of these solutions.

Information on the effect of bloody amniotic fluid during labor at term is scarce. This study assessed risk factors and obstetrical outcomes in labors complicated by bloody amniotic fluid. All nulliparas with singleton pregnancy, who underwent a trial of labor ≥37 weeks of gestation, in a single tertiary center, over six years were included. Obstetrical, delivery and neonatal outcomes were compared between deliveries with bloody amniotic fluid or clear amniotic fluid. Overall, 11,252 women were included. Among them, 364 (3.2%) had bloody amniotic fluid and 10,888 (96.7%) had clear amniotic fluid. Women with bloody amniotic fluid were characterized by shorter duration of the second stage of labor and higher rate of cesarean delivery due to non-reassuring fetal heart rate. The rates of cord pH < 7.1 and NICU admissions were also higher. In multivariate logistic regression analysis, cesarean delivery, cord blood pH < 7.1 and NICU admission were independently associated with increased odds ratio for bloody amniotic fluid. Bloody amniotic fluid at term is associated with adverse outcomes and must be considered during labor.

Due to their increased surface area, extent of swelling and active substance loading capacity and flexibility, nanogels made from natural and synthetic polymers have gained significant interest in the scientific and industrial areas. Especially, customized design and implementation of non-toxic, biocompatible, and biodegradable micro/nano carriers makes their usage very feasible for a range of biomedical applications, including drug delivery, tissue engineering, and bioimaging. The design and application methodologies of nanogels have been outlined in this review. Additionally, the most recent advancements in nanogel biomedical applications have been discussed, with a particular emphasis on applications for the delivery of drugs and biomolecules.

The anatomy and physiology of the eye strongly limit the bioavailability of locally administered drugs. The entrapment of therapeutics into nanocarriers represents an effective strategy to topically treat some ocular disorders, as they may protect the entrapped molecules, facilitating drug residence on the ocular surface and/or its penetration into different ocular compartments. The present work shows the activity of hyaluronan-cholesterol nanogels (NHs) as ocular permeation enhancers. Thanks to their bioadhesive properties, NHs firmly interact with the superficial corneal epithelium, without penetrating the stroma, modifying the transcorneal penetration of loaded therapeutics. Ex-vivo transcorneal permeation experiments showed that the permeation of hydrophilic drugs (i.e. tobramycin and diclofenac sodium salt), loaded in NHs, is significantly enhanced when compared to the free drug solutions. On the other side the permeation of hydrophobic drugs (i.e. dexamethasone and piroxicam) is strongly dependent on the water solubility of the entrapped molecules. The obtained results suggest that NHs formulations can improve the ocular bioavailability of the instilled drugs by increasing their preocular retention time (hydrophobic drugs) or facilitating their permeation (hydrophilic drugs), thus opening the route for the application of HA-based NHs in the treatment of both anterior and posterior eye segment diseases.

The purpose of current research work was to formulate and typify gelatin and poly(vinyl) alcohol (Gel/PVA) hydrogel which would be highly pH-responsive and can able to accomplish targeted delivery of methotrexate in order to treat the colo-rectal pathologies. The primed gel/pva hydrogel discs were subjected to various physicochemical techniques i.e. swelling, diffusion co-efficient, sol-gel analysis and porosity using three altered sorts of pH (1.2, 6.8 & 7.4) phosphate buffer solutions for assessment/evaluation, and their characterization was done through Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA). Shape alteration and controlled methotrexate of release of Gel/PVA hydrogel have been done using three type of pH (1.2, 6.8 & 7.4) phosphate buffer mediums. Methotrexate was loaded through in-situ drug loading method due to hydrophobicity. Different kinetic models (first order & zero order kinetic), Higuchi model and Krosmere peppas model/Power law were applied to manipulate the drug release data. Physicochemical evaluation tests and drug release profile results were found insignificant (p< 0.05) in various pH mediums and dependent upon polymers concentration pH of medium and cross-linker amount. Kinetic model disclosed that release of methotrexate from Gel/PVA hydrogel follow non-Fickian diffusion method. It became concluded from this research work that release of methotrexate Gel/PVA hydrogel in targeted colon area can be achieved for treating colo-rectal disorders.

A new variant of two-echelon routing problem is investigated, where the truck and the drone are used to cooperatively complete the deliveries of all parcels. The truck not only acts as a tool for parcel delivery, but also serves as a moving depot for the drone. The drone can carry several parcels and take off from the truck, while returning to the truck after completing the delivery. The energy consumption model for the routing process of the drone is analyzed, when it is utilized to deliver multiple parcels. A two-stage route-based modelling approach is proposed to optimize both the truck’s main route and the drone’s adjoint flying routes. A hybrid heuristic integrating nearest neighbor and cost saving strategies is developed to quickly construct a feasible solution. The simulated annealing algorithm is applied to improve the quality of the solution, where a Tabu list is employed to improve the search efficiency. Random instances at different scales are used to test the performance of the proposed algorithm. A case study based on the practical road network in Changsha, China, is presented, through which the sensitivity analysis is conducted with respect to some critical factors.

Drug delivery to the brain represents a challenge especially in the therapy of central nervous system malignancies. Simvastatin (SVT), as other statins, has shown potential anticancer properties that are difficult to exploit in the CNS. In the present work the physico-chemical, mucoadhesive and permeability enhancing properties of simvastatin-loaded poly-ε-caprolactone nanocapsules coated with chitosan for nose-to-brain administration were investigated. Lipid-core nanocapsules coated with different molecular weight (MW) chitosans (LNCchit) prepared by a novel one-pot technique were characterized for particle size, surface charge, particle number density, morphology, drug encapsulation efficiency, interaction between surface nanocapsules with mucin, drug release and permeability across two nasal mucosa models. Results show that all formulations present adequate particle size (below 220 nm), positive surface charge, narrow droplet size distribution (PDI<0.2) and high encapsulation efficiency. Nanocapsules presented controlled drug release and mucoadhesive properties dependent on the MW of the coating chitosan. The results of permeation across RPMI 2650 human nasal cell line evidenced that LNCchit increased the permeation of SVT. In particular, the amount of SVT permeated after 4h for nanocapsules coated with low MW chitosan, high MW chitosan and control SVT was 13.91 ± 0.78 µg, 9.15 ± 1.23 µg and 1.42 ± 0.21 µg respectively. These results were confirmed by the SVT ex vivo permeation across rabbit nasal mucosa. This study highlighted the suitability of LNCchit as promising strategy for the administration of simvastatin for a nose-to-brain approach for the therapy of brain tumors.

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.

In the field of nasal delivery, one of the most fascinating applications is the delivery of drugs directly to the central nervous system bypassing the blood brain barrier. This approach would provide a series of benefits, such as dose lowering and direct targeting of potent drugs, ultimately reducing their systemic side effects. Recently, clinical trials have explored the nasal administration of insulin for the treatment of Alzheimer’s disease, with promising results. The use of nanomedicines could provide further options for making nose-to-brain delivery reality. In particular, apart from the selection of devices able to deposit the formulation in the upper part of the nose, surface modification of these nanomedicines appears the key strategy to optimize the delivery of drugs from the nasal cavity to the brain. In this review, nanomedicines delivery approaches based on surface electrostatic charges, mucoadhesive polymers, as well as chemical moieties targeting nasal epithelium, will be discussed and critically evaluated for nose-to-brain delivery.

Objectives: The purpose of this study is to determine the association between umbilical venous blood flow (UVBF) to placental pulsatility index (PPI) ratio and gestational age (GA) in women undergoing prenatal assessments and adverse pregnancy outcome (APO) screening Methods: Between January and December 2022, sonographic examinations were conducted to assess the fetal umbilical cord insertion site in singleton fetuses, and hemodynamic indices of the umbilical artery, umbilical vein, and uterine artery were computed. Through regression analysis, we derived the optimal regression equation to elucidate the UVBF/PPI ratio parameters based on GA. Results: Among 492 singleton fetuses between 21+0 and 40+6 weeks of gestation in the final study. The average fetal UVBF/PPI ratio was 180.45±119.32. Correlation analysis revealed a positive relationship between the UVBF/PPI ratio and GA(p = .000). Using regression analysis, the best-fit regression equation was the linear function model, which explains the value of UVBF/PPI ratio parameters based on GA. Lower UVBF/PPI ratio revealed a positive relationship in the low birth weight fetuses (p=0.021) and higher preterm delivery rate (p=0.034). Cerebroplacental ratio (CPR) showed a high correlation with the UVBF/PPI ratio (r=0.471, p=0.000). Conclusions: The findings of our analyses revealed that contribute to our understanding of fetal hemodynamics and highlight the potential of UVBF/PPI ratio as a predictive marker for adverse pregnancy outcomes, such as preterm birth, low birth weight, or potential fetal hypoxemia. It might be useful for prenatal counseling and clinical purposes.

Extreme-mass-ratio inspirals (EMRIs) are significant observational targets for spaceborne gravitational wave detectors, namely, LISA, Taiji, and Tianqin, which involve the inspiral of stellar-mass compact objects into massive black holes with a mass range of approximately 104∼107M⊙. EMRIs are estimated to produce long lived gravitational wave signals with more than 105 cycles before plunge, making them an ideal laboratory for exploring the strong-gravity properties of the spacetimes around the MBHs, stellar dynamics in galactic nuclei, and properties of the MBHs itself. However, the complexity of the waveform model, which involves the superposition of multiple harmonics, as well as the high-dimensional and large-volume parameter space, make the fully coherent search challenging. In our previous work, we proposed a 10-dimensional search using Particle Swarm Optimization (PSO) with local maximization over the three initial angles. In this study, we extend the search to an 8-dimensional PSO with local maximization over both the three initial angles and the angles of spin direction of the MBH where the latter contribute a time independent amplitude to the waveforms. Additionally we propose a 7-dimensional PSO search by using a fiducial value for the initial orbital frequency and shifting the corresponding 8-dimensional Time Delay Interferometry responses until a certain lag returns the corresponding 8-dimensional log-likelihood ratio maximum. The reduced dimensionality likelihoods enable us to successfully search for EMRI signals with duration of 0.5 years and signal-to-noise ratio of 50 within a wider search range than our previous study. We discuss further developments, such as using a hierarchical search to narrow down the search ranges of certain parameters, and applying Graphics Processing Units to speed up the code. These advances aim to improve the efficiency and accuracy of the EMRI search algorithm.

In order to balance the conflicts among mass flow rate, total pressure ratio, adiabatic efficiency and stall margin in a low-bypass transonic fan, the optimization of the rotor blade is implemented in this study. An advanced 3D optimization design system is adopted, and flow diagnostic methods based on vorticity dynamics are employed to discuss the flow field. Results indicate that by controlling the blade camber line curvature, significant improvements in the aerodynamic performance for the fan stage are achieved, the total pressure ratio is increased by 1.90%, while the adiabatic efficiency and mass flow rate are increased by 4.45% and 5.82%, respectively. Vorticity diagnosis suggest that there exists a close link between performance parameters and vorticity parameters in the axial fan/compressor, both azimuthal vorticity and boundary vortex flux have significant influences on the stage performance. Moreover, the boundary layer separation is accompanied by the spike of entropy and static pressure, while the derivation/gradient of these flow parameters would also suffer drastic changes under the effect of shock wave. The vorticity parameters could provide detailed flow information about the on-wall flow with high accuracy, which provides the researchers with a novel method for the turbomachinery aerodynamic design and analysis.

Frontotemporal dementia (FTD) is the second most common form of presenile dementia; however, its diagnosis has been poorly investigated. Previous attempts to diagnose FTD using quantitative electroencephalography (qEEG) have yielded inconsistent results in both spectral and functional connectivity analyses. This study aimed to introduce an accurate qEEG marker that could be used to diagnose FTD and other neurological abnormalities. We used open-access electroencephalography data from OpenNeuro to investigate the power ratio between the frontal and temporal lobes in the resting state of 23 patients with FTD and 29 healthy controls. Spectral data were extracted using a Fast Fourier Transform in the delta (1–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–32 Hz), and gamma (32–45 Hz) bands. We found that the spectral power ratio between the frontal and temporal lobes is a promising qEEG marker of FTD. Frontal/temporal (F/T) theta/alpha, alpha/theta, al-pha/gamma, and gamma/alpha showed a consistently high discrimination score for the diagnosis of FTD for different parameters and referencing methods. The study findings can serve as reference for future research focused on diagnosing FTD and other neurological anomalies.

The objective of this study is to assess the hepatic/renal and splenic/renal echointensity ratios in ultrasonography in patients with and without diabetic nephropathy. This retrospective study included patients with diabetes mellitus who underwent ultrasound examinations at our hospital between January 2023 and May 2023. Ultrasound examinations done with renal cortical echogenicity and cortico-medullary differentiation by using B-mode ultrasonography. The hepatic/renal and splenic/renal echo intensity ratios were compared among study groups (diabetic patients with diabetic nephropathy and without nephropathy). The diabetic nephropathy group exhibited significantly higher right renal echointensity and left renal echointensity compared to the non-nephropathic group. Additionally, the splenic/renal echointensity ratio and hepatic/renal echointensity ratio were significantly lower in the diabetic nephropathy group. Urinary microalbumin levels was significantly correlated with Right renal echointensity (r=0.65, p&lt;0.001) and Left renal echointensity (r=0.69, p&lt;0.001). There was also a significant inverse correlation between urinary albumin and splenic/renal echointensity ratio (r=-0.58, p&lt;0.001). Ultrasonography, specifically the assessment of hepatic/renal and splenic/renal echointensity ratios, shows promise as a non-invasive and cost-effective method for evaluating morphological changes in the kidneys in patients with diabetic nephropathy. These findings suggest that ultrasonography can be a valuable tool for monitoring the progression of diabetic nephropathy and contributing to its early detection and management.

Background and aim: The albumin-globulin ratio (AGR) is one of the indicators of inflammation and immunity and it has a prognostic significance in many malignant diseases. Previous studies have shown the relationship between inflammatory mediators and POPF. This study aimed to evaluate the relation of AGR, which is a relatively new indicator, with postoperative pancreatic fistula (POPF). Methods: Pancreaticoduodenectomy (PD) patients between 2017 and 2020 were retrospectively analyzed and divided into two groups as those with and without clinically relevant POPF (CR-POPF). They were compared in terms of preoperative-postoperative AGR and clinicodemographic characteristics. AGR was calculated as Albumin / (Total protein-albumin) and the cutoff point for AGR was determined according to Youden’s index. Results: CR-POPF developed in 21% of 121 patients who underwent PD. There was no difference between the groups in terms of age, gender, comorbid disease status, pancreatic duct width, and anastomosis technique. Preoperative and postoperative day-3 (POD3) albumin levels and AGR were found to be significantly lower in the CR-POPF group. Multivariate analysis showed that AGR and pancreatic tissue stiffness are independent risk factors for the development of POPF. Conclusions: Low AGR is an independent risk factor for the development of CR-POPF. To reduce the incidence of POPF, this ratio should be tried to be kept at an optimal level.

Inorganic nanoparticles are utilized for therapeutic, diagnostic, or in combination, theranostic purposes. The latter involves simultaneous sensing, imaging, or tracking of drug delivery. Furthermore, these nanoparticles can differ in their morphologies, which affect outcomes such as the effectiveness of hyperthermia, induction, drug loading, circulation time by escaping the body's immune system, imaging modality clarity, and biosensing. However, design of these theranostics is limited by the lack of a method to predict their therapeutic efficacy. Herein, we report a simple and novel computational approach via algebraic and geometric calculations of surface area (SA) to volume (V) ratios (SA:V) which can help predict the efficacy of the inorganic nanoparticles of the investigated morphologies. The approach comprises a coding platform for the program and uses Python 3 on a Windows 10 operating system. Analyses of 29 polyhedral morphologies that inorganic nanoparticles could assume ex silico showed that only particular concave and convex morphologies in this size regime are more productive over the standard sizes as well as a few noted in literature for baseline comparison. Our results provide a method that can aid in predicting the efficacy of inorganic nanoparticles with certain morphology giving rise to their fundamental basis and eventual implementation ex silico.

A new covered yarn system is proposed in this manuscript by controlling the tension of the spandex elastic yarn drawing.. By analyzing the relationship between the draw ratio and yarn tension, it has been verified that the new tension controlled drawing system is feasible and results in yarns with superior quality and process stability.

Demographic and socio-economic developments couple with other requirements to satisfy human needs result in rapid urban expansion sometimes with increasing rate of surface extent greater than the rate of growth of population, that result in continuous sealing of ground surface thereby affecting ecosystem services. This study applied remote sensing toward achieving the progress of SDGs and stage to determine the ratio of the rate of land consumption to the rate of population growth of Gombe metropolis. QGIS 2.18 was used for the image processing and classification analysis for the key Landsat ETM+ (Enhanced Thematic Mapper), Impervious Surface Indices and population data to inform on the urban trend and LCR/PGR for the periods 2000-2005, 2005-2010, and 2010-2015. The result appears that the LCR/PGR for the periods of study show split trends. During 2000-2005 the result shows that the study area expanded outward with LCR/PGR of 1.2. The result also indicate that during 2005-2010, the study area densified with little expansion with the LCR/PGR of 0.8. The result further reveals that during 2010-2015 the LCR/PGR reached 1.8. Pointing that the study area expanded outward with the rate of ground sealing getting high.

We consider a model of predator-prey interaction at fractional-order where the predation obeys the ratio-dependent functional response and the prey is linearly harvested. For the proposed model, we show the existence, uniqueness, non-negativity as well as the boundedness of the solutions. Conditions for the existence of all possible equilibrium points and their stability criteria, both locally and globally, are also investigated. The local stability conditions are derived using the Magtinon's theorem, while the global stability is proven by formulating an appropriate Lyapunov function. The occurance of Hopf bifurcation around the interior point is also shown analytically. At the end, we implement the Predictor-Corrector scheme to perform some numerical simulations.

As a renewable industrial crop, Miscanthus offers numerous advantages, namely high photosynthesis activity (as a C4 plant) and exceptional CO2 fixation rate. These properties make Miscanthus very attractive for industrial exploitation, such as lignin generation. Here, we present a systematic study analyzing the correlation of the lignin structure with Miscanthus genotype and plant portion (stem versus leaf). Specifically, the ratio of the three monolignols and corresponding building blocks as well as the linkages formed between the units have been studied. Depending on the Miscanthus genotype and plant component (leaf versus stem), correlations between chemical structure and properties of the lignins have been determined, i.e. correlations in molecular weight, polydispersity and decomposition temperature. Lignin isolation was performed using non-catalyzed organosolv pulping and the structure analysis includes NREL, FTIR, UV-Vis, HSQC-NMR, TGA, pyrolysis GC/MS. Structural differences were found for stem and leaf-derived lignins. Compared to beech wood lignins, Miscanthus lignins possess lower molecular weight and narrow polydispersities (< 1.5 Miscanthus vs. > 2.5 beech) corresponding to improved homogeneity. In addition to conventional univariate analysis of FTIR spectra, multivariate chemometrics revealed distinct differences for aromatic in-plane deformations of stem versus leaf-derived lignins. These results emphasize the potential of Miscanthus as low-input resource and Miscanthus-derived lignin as promising agricultural feedstock.

The effect of the acetylene and hydrogen gases mixture ratios in direct low-temperature vacuum carburization was investigated. The gas ratio is an important parameter for producing the free radicals in the carburization. The free radicals can remove the natural oxide film by the strong reaction of the hydrocarbons, and then thermodynamically activity can be increased. When the gas ratio was below 1, the supersaturation expanded austenite layers were formed on the surface of the AISI 316L stainless steel, which had the maximum carbon solubility up to 11.5 at.% at 743 K, were formed. On the other hand, when the gas ratio was above 1, the carbon concentration of them remained low even if the process time was enough increased to reach the maximum carbon solubility. As a result, the carbon concentration underneath the surface was determined to be highly dependent on the gas mixture ratio of acetylene and hydrogen. In conclusion, it is necessary to restrict the ratio of acetylene and hydrogen gases to total mixture gases to form the expanded austenite layer with the high carbon concentration in the direct low-temperature vacuum carburization.

Purpose of Review Multipotent Mesenchymal stromal cells (MSCs) have recently risen to prominence in regenerative medicine for their powerful intrinsic properties of self-regeneration, immunomodulation, and multi-potency. They exhibited an excellent safety profile in early-phase clinical trials. Nevertheless, MSCs-based therapy suffers reduced efficacy in randomized clinical trials due to a poor understanding of their proper delivery modalities. Here, we intend to explore the current application of MSCs after tissue injuries. We specifically focus on tissue source, delivery routes, metabolic fitness, and cell dose. We further discuss potential approaches to optimize in vivo engraftment. Recent findings MSCs therapeutic effect mediates by paracrine and contact factors, which are cells' intrinsic physiological processes. The cell culture expansion process does not destroy MSCs' intrinsic properties. In vivo persistence of administered MSCs determines their therapeutic potency. Cell viability, fitness, immune match, and delivery route meticulously regulate their in vivo persistency. Different genetic or chemical modification strategies are currently applied to extend their in vivo lifespan and boost their pharmaceutical effect. Summary Improving the in vivo persistence of implanted MSCs could facilitate its clinical translation. This review highlights the pros and cons of different MSCs’ delivery strategies used in clinical or preclinical studies, emphasizing various modification approaches. These can promote prolonged graft cell survival.

The reproductive health of women is governed by an optimal balance between the host-microbiota interaction. Depletion in the beneficial vaginal microflora caused by depletion of Lactobacillus species and increased proliferation of pathogens results in gynecological infections. Among women of reproductive age, vaginal infections are increasingly prevalent. Attaining therapeutic efficacy using conventional formulations remains a challenge as vaginal fluids quickly remove or dilute the therapeutic formulations. Hydrogels have been widely exploited for targeted delivery of therapeutics directly into the vaginal mucus. With careful choice of polymers (natural, synthetic or semi-synthetic) hydrogels with specific properties such as stimuli-responsiveness, antimicrobial, and muco-adhesiveness can be tailored for higher therapeutic efficacy. In this review, the advnances in hydrogel strategies for the treatment of vaginal infections is presented with emphasis on the types and properties that play a significant role in vaginal drug delivery systems.

Nano-drugs and nano-delivery systems are rapidly evolving, with new strategies emerging in the current practices. The evolution of these technologies began with modifying the chemical structure, progressing to supramolecular ionic complexes, and culminating in elegant ad hoc delivery systems. Nanoparticles have numerous benefits as a carrier system for delivering therapeutic agents to intra-arterial sites. These benefits include their subcellular size, targeted surfaces, good suspensibility, and uniform dispersity, making them an ideal choice for catheter-based delivery. Despite the advancements made in the field of nano-drugs and nano-delivery systems, there are still some hurdles to overcome in terms of their commercial availability.The current review presents an updated summary of recent advancements in nano-drugs and nano-delivery systems, including their commercial availability. We aim to discuss the present challenges and prospects of commercially available nano-drugs and nano-delivery systems. Here, we provide a precise and informative overview of the current state of these technologies and underscore the potential they hold for future developments. Further, we have categorized commercially available modifications, name, parent company and their main applications in nano-drugs.

Carbon footprint mitigation actions have become a key issue for companies involved in urban freight transport. The electrification of the delivery fleets is one of the crucial sustainable actions carried out. To this end, it is necessary to explore several fleet renewal strategies over a finite planning horizon evaluating different types of electric powertrains for light commercial vehicles. The primary goal of this purpose-built analysis is to assist and boost the fleet managers' decisions when transitioning to alternative-fuelled vans, intending to maximize cost savings and reduce greenhouse gas emissions inventory. The model presented in this work is a Multi-Objective Linear Programming hybrid analysis taking into account the vehicle and energy supply infrastructure costs and the emissions reported in each inventory scope following the Greenhouse Gas Protocol sustainability guidelines. From this perspective, the conducted research offers a novel approximation to fleet management problems enabling a break-down cost analysis and an evaluation of the annual emissions company report. The comprehensive numerical simulations carried out over different study scenarios in Spain demonstrate that the optimization approach does not only show effective fleet renewal strategies but also identifies critical factors that impact the fleet's competitiveness, offering valuable insights for fleet managers and policymakers to meet carbon footprint reductions in a cost-effectively way.

mRNA vaccines have attracted widespread research attention with clear advantages in terms of molecular flexibility, rapid development, and potential for personalization. However, current mRNA vaccine platforms have not been optimized for induction of CD4/CD8 T cell responses. In addition, mucosal administration of mRNA based on lipid nanoparticle technology faces challenges in clinical translation. In contrast, adenovirus-based vaccines induce strong T-cell responses and have been approved for intranasal delivery. To leverage the inherent strengths of both the mRNA and adenovirus platforms, we developed a novel modular adenoviral mRNA delivery platform based on Tag/Catcher bioconjugation. Specifically, we engineered adenoviral vectors integrating Tag/Catcher proteins at specific locales on the Ad capsid proteins, allowing us to anchor mRNA to the surface of engineered Ad viruses. In proof-of-concept studies, the Ad-mRNA platform successfully mediated mRNA delivery and could be optimized via the highly flexible modular design of both the Ad-mRNA and protein bioconjugation systems.

Encapsulated nanofibers have emerged as a promising approach for the treatment of acne, owing to their ability to provide controlled release, targeted delivery, increased efficacy, and improved stability. Electrospinning is a well-established method for producing encapsulated nanofibers and has been shown to be effective for encapsulating various active ingredients. However, there are still several challenges that need to be addressed in the development of encapsulated nanofibers for acne treatment. One major challenge is the need for comprehensive in vitro and in vivo studies to evaluate the safety and efficacy of these treatments. The cost and scalability of production also need to be considered to make these treatments accessible and affordable for patients. In addition, the long-term stability of encapsulated active ingredients is another challenge in the development of encapsulated nanofibers for acne treatment. Regulatory frameworks need to be developed to ensure the safety and efficacy of these treatments. Future research may focus on developing multifunctional nanofibers that combine active ingredients with other properties, such as antimicrobial, anti-inflammatory, and wound-healing properties, to provide a comprehensive approach to acne treatment. Moreover, the development of nanofiber-based skincare products may have a significant impact on the cosmetic industry. Overall, while there are still challenges to overcome, the potential benefits of encapsulated nanofibers for acne treatment make them an exciting and promising area of research for the future. In particular, the integration of smart drug delivery systems and responsive materials may enable the development of more personalized and effective treatments for acne. The development of new materials and encapsulation techniques, as well as the exploration of combination therapies that target multiple aspects of acne pathogenesis, are also future perspectives for encapsulated nanofibers in acne treatment.

Purpose: The aim of this research was to prepare adhesive nanoparticles for the topical application of Minoxidil (MXD). Methods: Thiolated β-CDs were prepared via conjugation of cysteamine with oxidized CDs. MXD was encapsulated within thiolated and unmodified β-CDs. Nanoparticles (Thio-NP and blank NP) were prepared by ionic gelation of CDs with chitosan. Particle size and zeta potential were measured. FTIR analyses were performed for characterization of inclusion complex. Drug dissolution studies were carried out. An in vitro adhesion study over human hair was performed. An in vivo skin irritation study was performed. Ex vivo drug uptake was evaluated by using a Franz diffusion cell. Results: Thiolated β-CDs presented 1804.68 ± 25 μmol/g thiol groups and 902.34 ± 25 μmol/g disulfide bonds. Nanoparticles displayed particle sizes within a range of 231 nm to 319 nm. The zeta potential was in the range of ̶ 8.1 to + 12.0. FTIR analyses confirmed no interaction between the excipients and drug. Delayed drug release was observed from Thio-NP. Thio-NP retained over hair surfaces for a significantly longer time. Similarly, drug retention was significantly improved. Thio-NP displayed no irritation over rabbit skin. Conclusion: Owing to the above results, nanoparticles developed with MXD-loaded thiolated β-CDs might be a potential drug delivery system for topical scalp diseases.

In recent years, there has been an increasing demand for personalized experiences in various domains, including the cultural and educational sectors. Museums, as custodians of art, history, and scientific knowledge, are seeking innovative ways to engage their visitors and provide tailored content that enhances their understanding and appreciation of the exhibits. This article presents ExhibitXplorer, a distributed architecture service that leverages geofencing, artificial intelligence, and microservices to enable personalized content delivery in museums. By combining implicit and explicit segmentation of museum visitors and utilizing the GPT API for content generation, ExhibitXplorer offers a dynamic experience to different visitor segments, including researchers, students, casual visitors, and children. The system utilizes push notifications triggered by visitor location changes, allowing seamless delivery of personalized information both indoors and outdoors. Tests were conducted to evaluate the user experience of visitors to an outdoor ethnographic museum. The results showed that 55% of the test participants were satisfied and 45% very satisfied with the way personalized content was delivered.

Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Herein, we developed a novel method for the synthesis of uniformly sized microparticles via coaxial flow-phase separation. The study evaluated the effect of various process parameters on microparticle size and polydispersity including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution whereas surfactant concentration had the most substantial impact on the morphology of particles. Several microparticle formulations yielding particle sizes in the range of (5-50 µm), morphology, and concentration were synthesized as a demonstration of the tunability and scalability of this method. Notably, by controlling the process parameters microparticles of less than ~ 7 μm could be made using polymer concentrations varying by an order of magnitude. Finally, we demonstrated the tunability and scalability of this method by showing a 10-fold increase in encapsulation efficiency, a 3-fold increase in drug loading of a model hydrophilic drug, and modified release kinetics in microparticle formulations of comparable sizes but different polymer concentrations.

The role stakeholders play is fundamental to the realisation of sustainable development. Con-sequentially, there is need for the major stakeholders to be fully aware of their respective roles. Thus, this paper focused on assessing the Stakeholders roles in sustainable housing projects in Lagos State, Nigeria. Structured questionnaire survey was used to collect data from 259 stake-holders involved in sustainable housing projects in Lagos State, Nigeria. A total of 203 responses were obtained, representing 78% response rate. Primary data regarding the extent of stakeholders awareness of their roles in sustainable housing were collected. The data collected were analysed using mean ranking analysis and analysis of variance (ANOVA). The data collected were used to determine the extent of awareness of the stakeholders’ role in sustainable housing pro-jects in Lagos State, Nigeria. The results showed that all the stakeholders were aware of their respective roles in the delivery of sustainable housing projects and were highly conscious of them. Although their extent of awareness was at varying levels, there was no statistically significant difference of opinions amongst the different categories of stakeholders in the delivery of sustainable housing projects. The study concluded that Government and Project Managers have key roles to play as major stakeholders in the delivery of sustainable housing projects. The knowledge of the awareness of stakeholders’ roles in the delivery of sustainable housing project provides invaluable information to stakeholders regarding the important roles to focus attention on in achieving sustainable housing projects. The study provides a veritable basis for assessment of sustainable housing project in Lagos State, Nigeria.

Atopic dermatitis (AD) is a chronic eczematous inflammatory disease that may arise from environmental, genetic and immunological factors. Despite the efficacy of current treatment options like corticosteroids, such approaches are mainly focused on symptoms relief, and may present certain undesirable side effects. In recent years, investigation regarding isolated natural compounds, oils, mixtures and/or extracts, have gained scientific attention because of their high efficiency and moderate to low toxicity. Despite their promising therapeutic effects, the applicability of such natural health care solutions is somehow limited by their instability, poor solubility, and low bioavailability. Therefore, novel nanoformulation-based systems have been designed to overpass these limitations, thus enhancing the therapeutic potential, by promoting the capacity of these natural drugs to properly exert their action in AD-like skin lesions. For the best of our knowledge, this is the first literature review that focused on summarizing the last nanoformulation-based solutions loaded with natural ingredients, and specifically for the management of AD. We suggest that future studies should focus on robust clinical trials that may confirm the security and effectiveness of such natural-based nanosystems, thus paving the way for more reliable AD treatments.

One of the most frequent brain diseases, Alzheimer's is defined by poor cognitive function brought on by the build-up of Beta Amyloid plaques and the gradual death of neurons. Glucose metabolism and the development of amyloid plaques are being studied together. Under physiologically normal circumstances, glucose is the primary substrate for the adult human brain. The prodromal phases of AD are significantly influenced by glucose hypometabolism. Hypometabolism of glucose in the brain is a clear sign of mitochondrial dysfunction and bioenergetic system impairment. By regulating energy synthesis and cell death, mitochondria play a crucial role in the functioning of cells. Increased formation of reactive oxygen species (ROS) and oxidative stress are a result of mitochondrial dysfunction, which also accelerates the development of Alzheimer's disease. For the maintenance of balance, autophagy is crucial because it selectively destroys damaged mitochondria. AD affects this route for mitochondrial breakdown. Targeting specific mitochondrial ligands by interventions along this pathway might be a useful therapeutic approach. Due to a number of biological obstacles, this method has significant limitations. As a result, many nanocarriers have been created to improve drug delivery effectiveness. All potential nanotechnology-based treatments for AD have been examined in this study, with a particular emphasis on medication delivery to the mitochondria

Accruing evidence on the influence of β-carotene regarding the prevention of several chronic diseases - in addition to its well-acknowledged role in vision has been a strong driver for developing alternative delivery systems. Though oral delivery is accepted as the most fitting, mild and safe path for delivering bioactive agents, β-carotene delivery via food items poses challenges due to its lipophilic nature, poor water-solubility, high chemical/photochemical instability and poor oral bioavailability. Nanotechnology has opened new windows for delivering bioactive agents. Their physiochemical characteristics, i.e. small size, high surface area, unique composition, biocompatibility and biodegradability make these nanomaterials an attractive tool for β-carotene delivery. Delivering β-carotene through nanoparticles does not only improve its bioavailability/bioaccumulation in target tissues, but also lessens its sensitivity against environmental factors during processing. Regardless of these benefits, nanocarriers inherit some limitations, such as variations in sensory quality, modification of the food matrix, increasing costs, as well as limited consumer acceptance and regulatory challenges. This research area has been rapidly evolved, with a plethora of innovative nano-engineered materials, including micelles, nano/microemulsion, liposomes, niosomes, solid-lipid nanoparticles and nanostructured lipid carriers. These nano-delivery systems make conventional delivery systems appear archaic and promise better solubilization, protection during processing, improved shelf-life, higher bioavailability as well as controlled and targeted release. This review provides information on the state of knowledge on β-carotene nano-delivery systems adopted for developing functional foods: depicting their classification, composition, preparation methods, challenges, release-and absorption of β-carotene in the GIT and possible risks and future prospects.

Bacterial infections occur when wound healing fails to reach the final stage of healing, usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site accompanied very often by an increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies, such as polymers, scaffolds, films and wound dressings, organic and inorganic nanoparticles, to combat infection and modulate the healing rate have been discussed as well. New technologies such as CRISPR-Cas are taken into consideration as potential future tools for AMP delivery in skin therapy.

Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polysaccharide chitosan would improve the oral bioavailability of this drug. In this work, we produced IFNα-loaded chitosan nanoparticles by the ionotropic gelation method. Their size, size distribution and concentration were characterized by dynamic light scattering and nanoparticle tracking analysis. After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability of unmodified and PEGylated nanoparticles was measured in monoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated that the nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the oral pharmacokinetics in BalbC mice of nanoencapsulated IFNα revealed that it was absorbed reaching an area-under-the-curve of 56.9 pg.h/mL.

With the rapid progress of genetic engineering and gene therapy, World Anti-Doping Agency has alerted to gene doping and prohibited its use in sports. However, there is no standard method available yet for detection of transgenes delivered by recombinant adenoviral (rAdV) vectors. Here we aimed to develop a detection method for transgenes delivered by rAdV vectors in a mouse model that mimics gene doping. rAdV vectors containing mCherry gene was delivered in mice through intravenous injection or local muscular injection. After five days, stool and whole blood samples were collected, and total DNA was extracted. As additional experiments, whole blood was also collected from mouse tail tip until 15 days from injection of the rAdv vector. Transgene fragments from different DNA samples were analyzed using semi-quantitative PCR (sqPCR), quantitative PCR (qPCR), and droplet digital PCR (ddPCR). In the results, transgene fragments could directly be detected from blood cell fraction-DNA, plasma-cell free DNA and stool-DNA by qPCR and ddPCR, depending on specimen type and injection methods. We observed that a combination of blood cell fraction-DNA and ddPCR was more sensitive than other combinations used in this model. These results could accelerate the development of detection methods for gene doping.

Performance of flow through orifices on a perforated distribution pipe between periods with and without partial clogging (submersion of part of the distribution pipe) was compared. The distribution pipe directly receives runoff and delivers it to an underground infiltration bed. Partial clogging appeared in winter but reduced in summer. Performance was defined as flow rate divided by l_eff (h_(d,mean)^0.5) where h_(d,mean) is the mean pressure head that drives flow and l_eff is the effective pipe length (length of water column with pipe water volume and the pipe cross-sectional area). ANCOVA (ANalysis of COVAriance) was adopted to examine the clogging effects with flow rate plotted against l_eff (h_(d,mean)^0.5) . Partial clogging had a significant effect on pipe performance during periods of low or no rainfall. However, if only data during larger storms was considered, little evidence showed that partial clogging had effects on pipe delivery performance. Partial clogging might be caused by leaves accumulated in the lower section of the pipe in winter, and its effect was insignificant when water level rose in the pipe, utilizing significantly more orifices on the distribution pipe, thus the effect from the clogged portion had negligible impact on system performance. Larger storms might also provide the required flow rate to move the debris block thus exposing the orifices. Partial clogging did not increase the tendency of overflow; therefore, current maintenance schedule was sufficient to keep the distribution pipe at satisfactory performance even though partial clogging can exist.

To facilitate the computation of the uniaxial compressive strength value of the cemented paste backfill under the condition of high sand-cement ratio, and to analyze the size effect of the cemented paste backfill with high sand-cement ratio under varied aspect ratios, the cemented paste backfill specimens with sand-cement ratios of 8:1-24:1 and aspect ratios of 0.5, 1, and 2 were prepared. Through response surface experiments and finite element analysis, the influence of three aspect ratios on the cemented paste backfill strength was explored, and the failure characteristics and size effect mechanisms of cemented paste backfill with various aspect ratios were analyzed. The model of strength conversion between cemented paste backfill with different aspect ratios was established. The results show that the compressive strength of the cemented paste backfill decreases with the increase of the aspect ratio under the same mass concentration and sand-cement ratio. When the aspect ratio is 0.5 and 1, the splitting failure is the main factor; when the aspect ratio is 2, the shearing failure is the main factor. The three-dimensional stress caused by the end effect of the cemented paste backfill is the main reason for the high strength when the aspect ratio is 0.5. Due to the one-dimensional stress zone generated in the middle of the cemented paste backfill with an aspect ratio of 2 in the laboratory, its strength value is closer to the actual uniaxial compressive strength value of the cemented paste backfill. The strength values of the cemented paste backfill with aspect ratios of 0.5 and 1 were higher than the actual uniaxial compressive strength values in the laboratory. The rationality of the theoretical analysis was verified by the ABAQUS analysis results. According to the experimental results, a strength conversion model between different aspect ratios is established, which can provide a reference for the design of the uniaxial compressive strength of the cemented paste backfill.

Swarm intelligence (SI) methods are nature-inspired metaheuristics for global optimization that exploit a coordinated stochastic search strategy by a group of agents. Particle Swarm Optimization (PSO) is an established SI method that has been applied successfully to the optimization of rugged high-dimensional likelihood functions, a problem that presents the main bottleneck across a variety of gravitational wave (GW) data analysis challenges. We present results from a first application of PSO to one of the most difficult of these challenges, namely, the search for Extreme Mass Ratio Inspiral (EMRI) in data from future spaceborne GW detectors such as LISA, Taiji, or Tianqin. We use the standard Generalized Likelihood Ratio Test formalism, with minimal use of restrictive approximations, to search 6 months of simulated LISA data and quantify the search depth, in signal-to-noise ratio (SNR), and breadth, in the ranges of the EMRI parameters, that PSO can handle. Our results demonstrate that a PSO-based EMRI search is successful over a search region that is in the ballpark of the one that current hierarchical schemes can identify. Directions for future improvements, including computational bottlenecks to be overcome, are identified.

Background: The proportion of dietary protein may play a key role in the development of obesity in children and adolescents. Methods: Cross-sectional data of 4,336 children and adolescents from the National Health and Nutrition Survey (NHANES) during 2011 to March 2020 were analyzed. Multivariate logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals, and restriction cubic spline was uesd to explore nonlinear relationships of dietary protein energy supply ratio and obesity in children and adolescents. Results:In the adjusted logistic regression model, for every 1% increase in dietary protein energy ratio in children and adolescents, the increased risk of obesity was 4% (OR=1.04,95%CI:1.01-1.08). The restrictive cubic spline showed a nonlinear relationship between dietary protein energy ratio and obesity in children aged 6-11 years (P <0.05). The dietary protein energy supply ratio was included in the logistic regression model after converting to quartiles into categorical variables. The adjusted OR of children aged 6-11 years was 2.08 (95%CI:1.34, 3.23,P <0.01) for the highest quartile of dietary protein energy supply ratio compared with the lowest quartile. Conclusion: In American children, dietary protein energy supply ratios was positively correlated with obesity, independent of individual characteristics and energy.

During the last forty years, the use of strontium isotopes in archaeology and biogeochemical research has spread widely. These isotopes, alone or in combination with others, can contribute to trace past and present environmental conditions. However, the interpretation of the isotopic values of strontium is not always simple and requires good knowledge of geochemistry and geology. This short paper on the use of strontium isotopes is aimed at those who use this tool (archaeologists, but not only) but who do not have a thorough knowledge of mineralogy, geology, and geochemistry necessary for a good understanding of natural processes involving these isotopes. We report basic knowledge and suggestions for a correct use of these isotopes. The isotopic characteristics of bio-assimilable strontium depend not so much on the isotopic characteristics of the bulk rock as, rather, on that of its more soluble minerals. Before studying human, animal and plant remains, the state of conservation and any conditions of isotopic pollution should be carefully checked. Samples should be collected according to random sampling rules. The data should be treated by a statistical approach. To make comparisons between different areas, it should be borne in mind that the study of current soils can be misleading since the mineralogical modification of the soil over time can be very rapid.

A Savonius wind turbine is one of the simplest vertical-axis turbines. Several researchers have been attracted to it because of its simple structure, low noise, appropriate torque, and independence from wind direction. SR3345 and SR5050 blade profiles will be investigated for their effects on the performance of Savonius wind turbines. First, the fabricated wind turbine is placed in front of an open circuit wind tunnel with a velocity of 6 m/s. Furthermore, governing relationships are used to calculate power and torque coefficients as well as tip speed. In this study, the power and torque coefficients of the turbine are compared with the two profiles considered based on overlap ratios between 0 and 0.3. Despite its increased stability, the central shaft reduced the power coefficient of the turbine. For blade SR3345, the best performance occurs at tip speed ratios of less than 1, while for blade SR5050, the best performance occurs at higher tip speed ratios. Both blades SR3345 and SR5050 achieve the highest power coefficients at overlap ratios of 0 and 0.18 when a central shaft is present.

Propolis is known to have many benefits, especially in the health sector. Due to the sharp aroma &amp; taste, and the phenolic compounds contained in propolis are easily oxidized &amp; hydrolyzed at high temperatures, the application of propolis in the food sector is still lacking. Microencapsulation with a coacervation complex is used to overcome these problems. The thickness of the coating material is an important factor in the microencapsulation of complex coacervation. This study aimed to determine the coating ratio used to produce propolis microcapsules with the highest phenolic stability during storage and heating. This study consisted of three treatment ratios of whey protein isolate (WPI) &amp; pectin coating materials 1:2, 1:1, and 2:1. The results showed that the yield value ranged from 37.279-40.116%, aw 0.375-0.529, and encapsulation efficiency 85.45-96.44%. The color of the microcapsules produced was bright (L* = 94.28-95.35%), tended to be reddish (a* = 0.07-0.11) &amp; yellowish (b* = 4.36-4.83). The difference in the ratios treatment significantly affected the storage stability, while the heating stability ratio only significantly affected the 2:1 treatment. The best total phenolic stability of propolis microcapsules during storage &amp; heating was obtained by 1:1 treatment with retention values of 97.31% and 63.86%.

According to architectural standards, the common proportion of a rectangular-shaped classroom is the shallow proportion, which has a longer external room facade versus the perpendicular internal sides. Even in the Kingdom of Saudi Arabia (KSA), the same proportion is used in school projects. Environmentally, this proportion is logical when considering the role of adequate natural lighting for classroom visual functions, which could be more easily achieved if its longest side is the external one. But, the environmental efficiency of any architectural space cannot be only judged according to a single human comfort achievement, especially with the diverse environmental characteristics of places around the world. This diversity can show a defect in other human comfort achievements or other environmental issues in different ways when achieving a certain function in a unified way. A holistic study should be done for any common architectural shape or proportion to ensure their priority among other options in achieving maximum green architectural principles for a specific location before confirming and using it. The manuscript compares a rectangular classroom of different external/internal wall proportions to search for their preference to be used in Taif city schools in KSA. The compared case studies have different window variations and similarities to include their effect too. According to the overall green principles assessment, the results showed that the common proportion of classrooms didn’t give the higher green credits, which alerts us that the traditional rectangular classroom proportion is not always optimum for all regions including Taif city in KSA.

A developed six-port reflectometry (SPR) system was integrated to measure the relative permittivity of tumor and normal breast tissue for medical diagnostic purpose. In order to obtain an accurate and precise measurement, the calibration process was done to the SPR using the well-known three-standard technique. Next, the studied dielectric probe was connected to the calibrated measurement-port of the SPR. The open end of the probe aperture was dibbed into the normal and tumor synthetic breast tissue samples to measure the synthetic breast tissues dielectric constant, ɛrʹ, and loss factor, ɛrʺ in the frequency range of 1.5 GHz to 3.3 GHz. Finally, the comparative studies were conducted between commercial VNA with Keysight 85070E dielectric probe and the studied SPR-probe system based on the measured magnitude of the reflection coefficient, phase shift, dielectric constant, and loss factor of the synthetic breast samples. The maximum absolute errors of the measured reflection coefficient magnitude, phase shift, dielectric constant, and loss factor were found to be 0.01, 1.07°, 1.12, and 0.75, respectively. It was ascertained that the predicted dielectric constant, ɛrʹ, is able to differentiate between normal, (ɛrʹ &lt; 50) and tumor, (ɛrʹ &gt; 50) breast tissues.

An experimental ultra wideband ground penetrating radar based on Golay complementary sequences is proposed to locate underground pipes. Golay complementary sequences with the code length of 1024 and frequency of 1 GHz are used as the probe signals. Two-dimensional image of the buried pipes is achieved by correlation method and back projection algorithm. The experimental results show that both the plastic pipe and metallic pipe can be located with a range resolution of 10 cm. Furthermore, as the Golay complementary sequences are a pair of complementary sequences, the sum of their correlation function yields twice the value of the peak at the target position and zero elsewhere. Thus, compared with the stepped frequency signal radar or chaotic signal radar, the Golay-based radar can significantly improve the signal noise ratio and has capability of deep detection.

Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients.

This study investigates the pivotal areas where Artificial Intelligence (AI) integration in healthcare warrants further exploration, leveraging insights from Boston Specialists, a forefront healthcare provider in AI adoption. Employing a qualitative case study approach, enriched by in-depth interviews and comprehensive literature reviews, we identify three main domains for potential AI expansion: scheduling efficiency, clinical documentation, and AI-driven medical research. Our results underscore the substantial enhancements AI brings to operational workflows and patient care, notably through improved scheduling systems, accuracy in medical documentation, and the facilitation of data-driven research methodologies. These findings suggest a critical need for healthcare institutions to further invest in AI technologies, focusing on these key areas to harness AI's full potential in personalizing care, optimizing efficiency, and advancing medical knowledge. The study concludes with a call for continued investigation into AI's integration within healthcare settings, emphasizing the importance of a supportive organizational infrastructure, ethical considerations, and data security in realizing AI's transformative impact on healthcare delivery and patient outcomes.

Innovations in drug delivery systems are crucial for enhancing therapeutic efficiency. Our research presents a novel approach based on Electro-fluid dynamic atomization (EFDA) to fabricate core-shell monophasic particles (CSMp) from sodium alginate blends of varying molecular weights. This study explores the morphological characteristics of these particles in relation to material properties and process conditions, highlighting their potential in drug delivery applications. A key aspect of our work is the development of a mathematical model that simulates the release kinetics of small molecules, specifically sodium diclofenac. By assessing the diffusion properties of different molecules and gel formulations through transport and rheological models, we have created a predictive tool for evaluating the efficiency of these particles in drug delivery. Our findings underscore two critical independent parameters for optimizing drug release: the external shell thickness and the diffusivity ratios within the dual layers. This allows for precise control over the timing and intensity of the release profile. The study advances our understanding of EFDA in the fabrication of CSMp and offers promising avenues for enhancing drug delivery systems by tailoring release profiles through particle characteristic manipulation.

Lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy in recent years. The strategy of targeting immune cells in cancer therapy has become a research area of great interest. mRNA vaccines are a potential choice for tumor immunotherapy due to their ability to directly encode antigen proteins and stimulate a strong immune response. However, the mode of delivery and lack of stability of mRNA are key issues limiting its application. LNPs are an excellent mRNA delivery vector, and their structural stability and biocompatibility make them an effective means to deliver mRNA to specific targets. This study summarizes the research progress in LNP delivery vector-assisted targeted controlled release mRNA vaccines in tumor immunity. The role of LNPs in improving mRNA stability, immunogenicity and targeting is discussed. In addition, combined with the cutting-edge research results, the potential mechanisms and application prospects of LNP-mRNA vaccines in tumor immunotherapy were further analyzed. This review aims to systematically summarize the latest research progress in LNP delivery carrier-assisted targeted controlled-release mRNA vaccines in tumor immunity to provide new ideas and strategies for tumor immunotherapy and provide more effective treatment plans for patients.

Burden of diseases measured as disability-adjusted life years per 100,000 people can be mined from public domain data, when they are made available by population health surveillance systems. This can be analysed to allow insightful comparisons with the national average, and to understand differences in trends between the sexes, age groups, time periods, geographic regions and sub-regions. In this illustrative case study, we have analysed the Scottish burden of disease database to understand what ailed the population of the Grampian region before the COVID-19 pandemic. We have identified selected cancers, ischaemic heart disease, Alzheimer’s disease and other dementias amongst the highest contributors to the burden; that drug use disorders and colorectal cancer are showing worsening trends and require health promotion and disease prevention measures from ages 15 and 25 respectively, especially in Aberdeen City; and that males are more vulnerable to atrial fibrillation and flutter, diabetes mellitus and oesophageal cancer, while females are to cerebrovascular disease. We demonstrate the usefulness of our analysis and methodology for the wider health system, allowing targeted medical research investments and coordinated response from public health and health service delivery. We also show the need for up-to-date surveillance data, forecasts and evidence on the impact of interventions to be made available widely.

This article discusses the fabrication of pullulan/polyvinyl alcohol (PVA) and PVA blends as carrier polymers for drug delivery. This study utilized coaxial electrospinning to encapsulate doxorubicin (DOX), a common anticancer drug, within nanofibers, which helped mitigate the adverse effects of DOX on normal cells. The study also demonstrated that the coaxial electrospinning technique using PVA/pullulan cores was effective in inhibiting the attachment and proliferation of HeLa cells, a type of cervical cancer cell. The use of pullulan/PVA and PVA blends as carrier polymers in conjunction with coaxial electrospinning could provide a safe and effective drug delivery system for the treatment of cervical and other solid malignancies. The study concluded that nanofibers showed promising results in inhibiting the growth of HeLa cells, indicating their potential as safe and effective drug delivery systems for treating cervical cancer and other solid malignant tumors.

Populations with healthcare needs often reside in post-conflict settings where basic services needed to maintain good health may be non-existent or hard to access. Therefore, there is a need for better identification and reallocation of resources as part of the post-conflict health rehabilitation effort. This study applies an asset-based approach to explore the more optimal design of health services and to identify the resource constraints for basic health service delivery to the most vulnerable communities in eastern Congo. We implemented the asset mapping in two phases. Firstly, we combined a qualitative survey with community walks to identify the assets already present in the communities. Secondly, we conducted group discussions to map out assets that are the core of Asset-Based Community Development (ABCD) practice. We finally documented all assets in a Community Asset Spreadsheet. Overall, 209 assets were identified as available and potentially valuable resources for the communities in eastern Congo. Among them, 60 were local associations, 24 were land and physical environment, 43 were local institutions, 46 were individuals, 32 to economy and exchange, and only 6 were related to culture, history, and stories. Drawing upon the findings from the qualitative survey, community walks, and group discussions, we conclude that an important number of resources were in place for basic health service delivery. By activating the existing and potential resources, the most vulnerable populations in eastern Congo might have the required resources for basic health service delivery. Our findings support the use of an asset-mapping research method as appropriate to identify existing and potential resources for basic health services in a post-conflict setting.

Keywords: Antisense Oligonucleotides, Cell Penetrating Peptides, Delivery, DG9 peptide, Phosphorodiamidate morpholino oligomers (PMO), Pip, R6G.

Dendritic Mesoporous Organosilica Nanoparticles (DMON) are a new class of biodegradable nanoparticles suitable for biomolecules delivery. In order to escape from the endosomes-lysosomes and to deliver biomolecules in the cytoplasm of cells, we studied photochemical internalization (PCI) and photodynamic therapy (PDT) of DMON. We added photosensitizers in the framework of DMON. DMON were also loaded with siRNA or FVIII factor protein. We made four formulations with four different photosensitizers, The photosensitizers allowed to perform imaging of DMON in cancer cells, but the presence of the tetrasulfide bond in the framework of DMON quenched the formation of singlet oxygen. Fortunately one formulation allowed to efficiently deliver proapoptotic siRNA in MCF-7 cancer cells leading to 31% of cancer cell death, without irradiation. For FVIII protein, it was loaded in two formulations with drug loading capacities (DLC) up to 25%. In conclusion DMON are versatile nanoparticles which allowed to load siRNA and to deliver it in cancer cells, and to load FVIII protein with good DLC. Due to the presence of tetrasulfide, it was not possible to perform PDT and PCI.

Mucosal vaccines offer several advantages over injectable conventional vaccines, such as adaptive immunity induction, secretory IgA production at the entry site of most pathogens, and needleless vaccinations. Despite their potential, only a few mucosal vaccines are currently used. Developing new effective mucosal vaccines strongly relies on identifying innovative anti-gens, efficient adjuvants, and delivery systems. Several approaches based on phages, bacteria, or nanoparticles have been proposed to deliver antigens to mucosal surfaces. Bacterial spores have also been considered antigen vehicles, and various antigens have been successfully exposed on their surface. Due to their peculiar structure, the spores conjugate the advantages of live microorganisms with synthetic nanoparticles. When mucosally administered, spores expressing anti-gens have been shown to induce antigen-specific, protective immune responses. This review accounts for recent progress in the formulation of spore-based mucosal vaccines, describing the spore's structure, specifically the spore surface, and the diverse approaches developed to improve its efficiency as a vehicle for heterologous antigen presentation.

Lipid nanoparticles have an interesting part of drug delivery system. In this study, the modification of the convention nano-lipid based soybean lecithin was demonstrated. Ginger oil derived Zingiber officinale was used along with lecithin, cholesterol and span 80 to fabricate nano-lipid (GL nano-lipid) using thin-film method. Through TEM and confocal microscope, GL nano-lipid exposes the liposome- like morphology. The average size of the resultant nanoparticles was 249.1nm with monodistribution (PDI= 0.021). The ζ-potential of GL nano-lipid was negative as similar to as prepared nano-lipid based lecithin. GL nano-lipid express the highly stable over 60 days of storage at room temperature in term of size, ζ-potential. A shift of pH value from alkaline to acid was detected in lecithin nano-lipid, while with the incorporation of ginger oil, pH value of nano-lipid dispersion was around 7.0. Furthermore, due to the rich of shogaol-6 and other active compounds in ginger oil, the GL nano-lipid is endowed with intrinsic antibacterial feature. In addition, the sulforhodamine B (SRB) assay and live/dead imaging revealed the excellent biocompatibility of GL nano-lipid. Notably, GL nano-lipid was capable to carry the hydrophobic agents as curcumin and perform a pH-dependent release profile. A subsequent characterization are a suitable potential for drug delivery system.

The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape from lysosomal destruction. Most of artificial nanocarriers suffer from intrinsic limitations that either prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and extracellular vesicles. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into extracellular vesicles.

Skeletal myopathy encompasses both atrophy and dysfunction and is a prominent event in cancer and chemotherapy-induced cachexia. Here, we investigate the effects of chemotherapeutic agent, 5-fluorouracil (5FU), on skeletal muscle mass and function, and whether small molecule therapeutic candidate, BGP-15, could be protective against the chemotoxic challenge exerted by 5FU. Additionally, we explore the molecular signature of 5FU treatment. Male Balb/c mice received metronomic tri-weekly intraperitoneal delivery of 5FU (23 mg/kg), with and without BGP-15 (15 mg/kg), 6 times in total over a 15-day treatment period. We demonstrated that neither 5FU, nor 5FU combined with BGP-15, affected body composition indices, skeletal muscle mass or function. Adjuvant BGP-15 treatment did, however, prevent the 5FU-induced phosphorylation of p38 MAPK and p65 NF-κB subunit, signalling pathways involved in cell stress and inflammatory signalling, respectively. This as associated with mitoprotection. 5FU reduced the expression of the key cytoskeletal proteins, desmin and dystrophin, which was not prevented by BGP-15. Combined, these data show that metronomic delivery of 5FU does not elicit physiological consequences to skeletal muscle mass and function but is implicit in priming skeletal muscle with a molecular signature for myopathy. BGP-15 has modest protective efficacy against the molecular changes induced by 5FU.

We consider the problem of scheduling $n$ jobs with identical processing times and given release as well as delivery times on $m$ uniform machines. The goal is to minimize the makespan, i.e., the maximum full completion time of any job. This problem is well-known to have an open complexity status even if the number of jobs is fixed. We present a polynomial-time algorithm for the problem which is based on the earlier introduced algorithmic framework blesscmore (``branch less and cut more''). We extend the analysis of the so-called behavior alternatives developed earlier for the version of the problem with identical parallel machines and show how the earlier used technique for identical machines can be extended to the uniform machine environment if a special condition on the job parameters is imposed. The time complexity of the proposed algorithm is $O(\gamma m^2 n\log n)$, where $\gamma$ can be either $n$ or the maximum job delivery time $q_{\max}$. This complexity can even be reduced further by using a smaller number $\kappa<n$ in the estimation describing the number of jobs of particular types. However, this number $\kappa$ becomes only known when the algorithm has terminated.

Background: The use of technology in paediatrics is increasing, and new health technology will change the way in which paediatric care is delivered in the future. This review is part of the Royal College of Paediatrics and Child Health Paediatrics 2040 project, which is developing a credible vision for the future of paediatrics in the UK. Aims: To summarise the impact of health technology on the delivery of paediatric care over the last ten years. To learn from existing technology use and make recommendations for future implementation. Methods: A search strategy was developed and two databases (Cochrane Library and PubMed) were systematically searched in August 2019 for relevant publications in English. Searches were limited to papers published between January 2009 and August 2019 (with further rapid review of papers published between September 2019 and November 2020). We included papers that studied young people up to the age of 24 or on those providing care for this population. A thematic synthesis of the data from the included studies was undertaken using seven domains of paediatric care. Results: 128 studies were included, grouped by domain of care. Most included studies were defined as digital (n=55) or communication (n=37). Studies looked at the different types of health technology used within different domains of care, including secondary and tertiary care (n=39), public health and prevention (n=29), and community (n=20). Studies were assessed on delivery of care outcomes using positive, negative, mixed and no effect. The most common outcomes reported were adherence and satisfaction. Discussion: This review highlights the growing importance of technology in delivering paediatric care. Six themes emerged: the importance of clear guidelines, continuity of care, confidentiality and privacy, digital poverty, using a personalised approach, and using technology to supplement rather than replace. In future, technology development should involve the end user throughout the design process.

Bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally but oral delivery is highly advantageous for immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in PBS, containing Tween 80, with and without the addition of mannitol or trehalose. Samples were frozen at -20oC, freeze-dried and the lyophilised powders were compressed to produce BCG-Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in SIF within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.

(1) Background: Premature infants require mothers’ milk fortification to meet nutrition needs, but breast milk composition may be variable leading to a risk of inadequate nutrition. We aimed at determining factors influencing mothers’ milk macronutrients. (2) Methods: Milk samples were analyzed for the first 5 weeks after premature delivery, by infrared spectroscopy. Mothers’ nutritional intake data were obtained during standardized interviews with dieticians then analyzed with reference software. (3) Results: Composition of 367 milk samples from 81 mothers was (Median [range]g/100mL): Carbohydrates 6.8[4.4-7.3], lipids 3.4[1.3-6.4], proteins 1.3[0.1-3.1]. There was a relationship of milk composition with mothers’ carbohydrates intake only (r=0.164; p<.01). Postnatal age was correlated with milk proteins (r=-0.505 p<.001) & carbohydrates (r=+0.202, p<.001). Multiple linear regression analyses showed (coefficient) a relationship between milk proteins r=0.547 and postnatal age (-0.028), carbohydrates intake (+0.449) and the absence of maturation (-0.066); and between milk lipids r=0.295 and carbohydrates intake (+1.279) and smoking (-0.557). Finally, between milk carbohydrates concentration r=0.266 and postnatal age (+0.012) and smoking (-0.167). (4) Conclusions: Variability of mothers’ milk composition is differentially associated for each macronutrient with maternal carbohydrates intake, antenatal steroids, smoking, and postnatal age. Improvement in milk composition could be achieved by modification of these related factors.

TThe number of supermarkets offering a grocery delivery has been increasing during the last years. Many studies deduce CO₂ emission savings using this concept. Since the delivery of groceries also consumes energy and produces emissions, break-even points can be calculated, from where the delivery has environmental advantages compared to the customer pickup. In this paper, influences of differing vehicle use on break-even points for savings of energy and CO₂ emissions are analyzed for the case of Haidhausen Süd, a city district of Munich in Germany. Internal combustion engine and electric vehicles are investigated to depict current as well as future trends. After an introduction to the used methodology, the potential to save energy and CO₂ emissions related to the delivery of groceries in the chosen district of Munich is evaluated. Afterwards, influences on the break even points are presented and discussed. As the results show, a delivery of groceries leads to energy and carbon dioxide savings in a wide range of private vehicle use for grocery shopping trips. Nevertheless, if the complete customer vehicle fleet is electrified, the use of delivery vehicles with an internal combustion engine can cause an additional environmental impact at the current modal split for shopping trips in Germany.

Curcumin is a promising anti-cancer drug but its applications in cancer therapy are limited due to its poor solubility, short half-life and low bioavailability. In this study, curcumin loaded magnetic alginate / chitosan nanoparticles were fabricated to improve the bioavailability, uptake efficiency and cytotoxicity of curcumin to MDA-MB-231 breast cancer cells. Alginate and chitosan were deposited on Fe3O4 magnetic nanoparticles based on their electrostatic properties. The sizes of the nanoparticles (120-200 nm) were within the optimum range for drug delivery. Sustained curcumin release was obtained use the nanoparticles with the ability to control the curcumin release rate by altering the number of chitosan and alginate layers. Confocal fluorescence microscopy results showed that targeted delivery of curcumin with the aid of magnetic field were achieved. The FACS assay indicated that MDA-MB-231 cells treated with curcumin loaded nanoparticles had a 3-6 folds uptake efficiency to those treated with free curcumin. MTT assay indicated that the curcumin loaded nanoparticles exhibited significantly higher cytotoxicity toward MDA-MB-231 cells than toward HDF cells. The sustained release profiles, enhanced uptake efficiency and cytotoxicity to cancer cells as well as the targeting potential make MACPs a promising candidate for cancer therapy.

In this study, the impact of the addition of high-aspect-ratio nano-ettringite to photocurable epoxy acrylate resin was explored, with a specific focus on the changes observed in viscosity, shrinkage, tensile strength, and elongation at the break of composites formed. Herein, the nano-ettringite samples were modified using KH-570. The 3 wt% or 6 wt% KH-570-modified and unmodified nano-ettringite were dispersed into the resin by ultrasonic treatment in conjunction with mechanical stirring. The grafting effects of nano-ettringite onto KH-570 were analyzed through scanning electron microscopy (SEM), X-ray diffraction (XRD), thermogravimetric (TG) analysis, and Fourier transform infrared spectroscopy (FTIR). The results demonstrate that increased dosages of unmodified and modified nano-ettringite led to increased viscosity of the composite while reducing shrinkage. At the same dosage, the photocurable resin with modified nano-ettringite demonstrated a lower shrinkage and a higher tensile strength. Notably, when the amount of modified nano-ettringite was 3 wt%, the highest tensile strength of the composite was 64.61 MPa, presenting a 72.57% increase compared to the blank sample. Furthermore, the incorporation of modified nano-ettringite as a filler provides a new perspective for improving the performance of photocurable epoxy acrylate resin composites.

Manufactured sand and natural sand have great differences in terms of physical properties, chemical composition, and so on. In the mix ratio design of manufactured sand concrete, the traditional common concrete ratio cannot be used. The water-cement ratio playing a crucial role in the mix ratio design. The optimum water-cement ratio can not only improve concrete performance, it can also reduce cement consumption and costs. The present study examines the working performance indicators and mechanical performance indicators of manufactured sand concrete using Fujian granite with three strength grades (C35, C40 and C50) at different water-cement ratios. The impact of water-cement ratio on the operational and mechanical performance of manufactured sand concrete with different strength grades is analyzed and summarized. Revised sentence: The findings suggest that the workability of Fujian granite concrete is directly influenced by the water-cement ratio. Additionally, the water-cement ratio indirectly affects the mechanical properties of manufactured sand concrete. Finally, when changing the water-cement ratio, cube compressive strength, splitting tensile strength and bending strength exhibit similar trends. The optimal water-cement ratio for C35 concrete is determined to be 0.39, considering the workability and mechanical properties of Fujian granite manufactured sand concrete. Similarly, the optimal water-cement ratio for C40 concrete is 0.34, while for C50 concrete it is 0.32.

The present study illustrates the strong effect of geometrical parameters on the magneto-structural properties of Co2MnSi glass-coated microwires prepared using the Taylor-Ulitovsky method. Thus, two samples with different geometrical aspect ratios (ρ= d / D) have been fabricated, where d is the metallic nuclei diameter and D is the total diameter of the Co2MnSi microwire. The XRD analysis shows a significant change by modifying the aspect ratio, for ρ = 0.46 the main peak with miller indices (220) is recognized as an A2-type disordered cubic structure. Meanwhile, in the sample with a low aspect ratio, ρ = 0.31, the perfect L21 ordered cubic structure is attained. In addition, a decrease in average grain size from 36.62 nm to 28.07 nm by increasing the aspect ratio from 0.46 to 0.31 is observed. The magnetic characterization has been done in a wide range of temperatures and magnetic fields. Both of Co2MnSi samples show ferromagnetic behavior in a whole measuring temperatures range. A significant increase in coercivity and normalized reduced remanence by decreasing the aspect ratio is observed. The change in the magnetic properties is attributed to the modification in the microstructure, which is induced during the fabrication process. Such a dependence on the microstructure and magnetic properties on the ρ-ratio can be associated either with the internal stresses distribution and magnitude or with different quenching rates of microwires with different aspect ratios. The current findings demonstrate the tunability of microstructure and magnetic properties of Co2MnSi-glass-coated microwires simply, by a small modification in the geometric properties during the manufacturing process and without excreting any additional post-processing. The variation in geometric parameters of Co2MnSi glass-coated microwires allows us to tune magnetic properties and structure, which is essentially advantageous for sensing devices development.

Our matter universe is made up of four components of dark energy (DE), dark matters (DMs), leptons and quarks which are created from the decay of the primary black hole through the inflation after big bang. In the three-dimensional quantized space model, the sum (DER) of the dark energy (DE) and radiations (R) is the flat photon space and there are 39 particles of 3 dark matters, 9 leptons and 27 quarks. Generally speaking, the mass ratio of the quarks with the 27 particles is smallest and the mass ratio of the DER photon space with the 1 massless photon is largest. Therefore, the mass ratios of DER, DMs, leptons and quarks are inversely proportional to the particle numbers of DER, DMs, leptons and quarks as the first assumption. This simple rule is called as the universe mass ratio golden rule in Fig. 12. This simple rule is successfully applied to the observed mass ratios of the Planck and WMAP missions. The best particle number combination (1, 3, 9, 27) of the four components (DER, DMs, Leptons, Quarks) to explain the Planck 2018 and WMAP results is the same as the particle number combination (1, 3, 9, 27) of the 3-dimensional quantized space model. The calculated mass ratios of DER, DMs, leptons and quarks are 67.5 %, 22.5 %, 7.5 % and 2.5 %, respectively. And the calculated mass ratios of neutrinos and ordinary matters are 5.0 % and 5.0 %, respectively. The mass ratios of the dark energy (68.47(23) %) and matters (31.53(23) %) obtained from the Planck 2018 results are consistent with the calculated mass ratios of the DER (67.5 %) and matters (32.5 %). The mass ratio of the dark energy (72.1(15) %) obtained from the WMAP 9 year results is explained as the summed mass ratio (72.5 %) of DER (67.5 %) and neutrinos (5.0 %). The universe evolution including the super-massive black holes (SMBHs) is shown in Fig. 4. The accelerated space expansion of our universe requires the addition of the new dark energy. If this new dark energy is added, the mass ratio of the dark energy is a little bit increased. The difference (0.97 %) between the observed value (68.47(23) %) and calculated value (67.5 %) is explained by adding the new dark energy in Figs. 2, 4, 7, 8, 9, 10 and 11. The corrected mass ratios of DER, DMs, leptons and quarks are 68.47 %, 21.8286 %, 7.2762 % and 2.4254 %, respectively. The corrected mass ratios of the neutrinos (called as cosmic background neutrinos) and ordinary matters (OMs) are 4.8508 % and 4.8508 %, respectively. These corrected mass ratios can explain the mass ratios obtained from the WMAP and Planck missions. In other words, the mass ratios calculated from the best particle number combination support the elementary particles, dark matters and dark energy (photon space) proposed by the three-dimensional quantized space model based on the 10-D Euclidean space.

Al-6%Mg-Sc-Zr alloys with the total ratio of Sc + Zr = 0.32 wt.% make up the target of this research. The content of scandium and zirconium varied with an increment of 0.02%. The alloys were produced by induction casting. Their ultrafine-grained (UFG) microstructure was formed with Equal Channel Angular Pressing (ECAP). Such cast alloys have a homogeneous macrostructure formed by small equiaxed grains in the central part of the ingot and columnar crystals along the edges of the cross section. After ECAP, the average grain size in the alloy specimens is 0.5–1 µm. The average grain size does not depend on the ratio of Sc and Zr in these alloys. Superplasticity tests were performed at temperatures ranging from 300 to 500 °C and at a strain rate varying between 3.3·10-3 and 3.3·10-1 s-1. UFG Al-6%Mg-0.20%Sc-0.12%Zr and Al-6%Mg-0.18%Sc-0.14%Zr alloys exhibit the highest superplasticity. It was suggested that changes in Sc:Zr ratio affect spatial distribution and composition of the following precipitating particles: Al3Sc, Al3Zr, Al3(ScxZr1-x). An increase in Zr concentration is shown to reduce the susceptibility of UFG alloys to cavitation fracture.

In the human organism various carotenoids are present of which, some are retinoid precursors. The bioactive derivatives of these retinoids are the retinoic acids, which can potently activate nuclear hormone receptors like the retinoic acid receptor and the retinoid X receptor. In our study using an HPLC analytical approach we aimed to assess how plasma carotenoid and retinoid concentrations along with the ratio of their isomers are altered in atopic dermatitis (AD) patients (n=20) compared to healthy volunteers (HV, n=20). We found that plasma levels of the carotenoids lutein (HV 198 ± 68 ng/ml, AD 158 ± 57 ng/ml), zeaxanthin (HV 350 ± 142 ng/ml, AD 236 ± 85) as well as the retinoids retinol (HV 216 ± 89 ng/ml, AD 167 ± 76 ng/ml) and all-trans-retinoic acid (HV 1.1 ± 0.6 ng/ml, AD 0.7 ± 0.5 ng/ml) were significantly lower in AD-patients, while lycopene, α-carotene and β-carotene levels were comparable. In addition the ratios of 13-cis vs. all-trans lycopene as well as 13-cis vs. all-trans retinoic acid were increased in the plasma of AD-patients indicating an AD-specific 13C-isomerisation. A positive correlation with SCORRAD was calculated with 13-cis vs. all-trans lycopene ratio, while a negative correlation was observed with zeaxanthin plasma levels. Based on our results we conclude that in the plasma of AD-patients various carotenoids and retinoids are at lower levels, while the ratio of lycopene isomers was also altered. The higher rate of lycopene and retinoic acid isomerisation products might be a consequence of AD or might result in an altered activation of nuclear hormone receptor signaling pathways and thus maybe partly be responsible for the AD-phenotype and additionally may represent a good plasma marker for AD.

All empirical water column correction methods have consistently been reported to require existing depth sounding data for the purpose of calibrating a simple depth retrieval model; they yield poor results over very bright or very dark bottoms. In contrast, we set out to (i) use only the relative radiance data in the image along with published data, and several new assumptions, (ii) in order to specify and operate the simplified radiative transfer equation (RTE), (iii) for the purpose of retrieving both the satellite derived bathymetry (SDB) and the water column corrected spectral reflectance over shallow seabeds. Sea truth regressions show that SDB depths retrieved by the method only need tide correction. Therefore it shall be demonstrated that, under such new assumptions, there is no need (i) for formal atmospheric correction, (ii) nor for conversion of relative radiance into calibrated reflectance , (iii) nor for existing depth sounding data, to specify the simplified RTE and produce both SDB and spectral water column corrected radiance ready for bottom typing. Moreover, the use of the panchromatic band for that purpose is introduced. Altogether, we named this process the Self-Calibrated Supervised Spectral Shallow-sea Modeler (4SM). This approach requires a trained practitioner, though, to produce its results within hours of downloading the raw image. The ideal raw image should be a “near-nadir” view, exhibit homogeneous atmosphere and water column, include some coverage of optically deep waters and bare land, and lend itself to quality removal of haze, atmospheric adjacency effect, and sun/sky glint.

The unprecedented production and sharing of data, opinions, and comments among people on social media and the Internet in general has highlighted sentiment analysis as a key machine learning approach in scientific and market research. Sentiment analysis can extract sentiments and opinions from user-generated text, providing useful evidence for new product decision-making and effective customer relationship management. However, there are concerns about existing standard sentiment analysis tools regarding the generation of inaccurate sentiment classification results. The objective of this paper is to determine the efficiency of off-the-shelf sentiment analysis APIs in recognizing low-resource languages, such as Greek. Specifically, we examined whether sentiment analysis performed on 300 online ordering customer reviews using the Meaning Cloud web-based tool produced meaningful results with high accuracy. According to the results of the study, we found low agreement between the web-based and the actual raters in the food delivery services related data. However, the low accuracy of the results highlights the need for specialized sentiment analysis tools capable of recognizing only one low-resource language. Finally, there is a significant need for the creation of industry-specific lexical resources that provide decision-makers with valuable insights.

Currently the bimatoprost implant (DURYSTA) is approved for a single administration secondary to concern for progressive corneal endothelial cell (CEC) loss with intracameral administration. In order to better understand the cause of CEC loss and other adverse events (AEs) with intracameral administration, multimodal imaging of the implant utilizing optical coherence topography (OCT), robotic ultrasound and bio microscopy video recording was utilized. Inherently the anterior chamber is a non-confined space. In certain examples the implant assumed a round and spotted structure as it picked up iris pigment as it migrated around the anterior chamber. Accordingly, we explored delivery of the implant in the middle segment behind the iris and in front of the pseudophakic lens. We then evaluated the suitability of various imaging modalities to assess the implant in this location. For middle segment administration, the ArcScan Insight 100 robotic ultrasound provided resolution and repeatability sufficient to monitor the implant behind the iris. This preliminary study hypothesizes that DURYSTA migration in the anterior chamber is the main source of AEs. Through use of a confined location, the middle segment, the implant is unlikely to migrate and cause CEC loss while also delivering drug closer to its site of action, the ciliary body. Further efforts are underway to understand the suitability of the middle segment for serial DURYSTA administration to maximize intraocular pressure lowering while minimizing AEs.

Polyelectrolyte multilayers (PEMs) deposited on porous composite polylactic acid/poly(ε-caprolactone) substrates were studied. The substrates were previously charged in a corona discharge. Time dependences of the normalized surface potential for positively and negatively charged electrets were investigated. The morphology of the obtained porous substrates was examined by means of scanning electron microscopy (SEM). The chitosan and the casein polyelectrolytes were deposited on the substrates using the layer-by-layer (LbL) technique. A drug loading efficiency and the release kinetics were determined spectrophotometrically.

A large body of evidence, replicated in many mouse models of Alzheimer Disease (AD), demonstrated the therapeutic efficacy of oral rapamycin. Administration of m-TOR inhibitors (mTOR-Is), early after the clinical onset, greatly diminished cognitive impairment, amyloid angiopathy, intracellular beta Amyloid and neurofibrillary tangles load. The daily intake of rapamycin has always been 2.24g/Kg/24h. In humans the maximal tolerated oral dose is a few milligrams/day, and at this dosage patients are severely immunosuppressed. Thanks to rapalogs’ scarce CNS-related side effects, we administered intracerebroventricularly (ICV) high doses of the mTOR-I everolimus in a mouse model of AD (3xTg-AD) without significant systemic effects. The instability of the liquid formulation at body temperature (BT) made the treatment very short. Nevertheless, the efficacy of the treatment was high and much longer lasting than expected. In order to set up a thermostable, translational liquid formulation of mTOR-Is, we loaded everolimus in distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) micelles by the thin layer method. The formulation we obtained maintained over 95% of activity after 14 days at BT. We can envision short, potentially periodic ICV treatments in AD patients which replicate results obtained on animal models. The treatment could benefit also Tuberous Sclerosis and Multiple Sclerosis patients.

The key challenges to treating glioblastoma multiforme (GBM) are the heterogenous and complex nature of the GBM tumour microenvironment (TME) and difficulty of drug delivery across the blood-brain barrier (BBB). The TME is composed of various neuronal and immune cells, as well as non-cellular components including metabolic products, cellular interactions, and chemical compositions, all of which play a critical role in GBM development and therapeutic resistance. In this review, we aim to unravel the complexity of the GBM TME, evaluate current therapeutics targeting this microenvironment, and lastly identify potential targets and therapeutic delivery vehicles for the treatment of GBM. Specifically, we explore the potential of aptamer-targeted delivery as a successful approach to treating brain cancers. Aptamers have emerged as promising therapeutic drug delivery vehicles with the potential to cross the BBB and deliver payloads to GBM and brain metastases. By targeting specific ligands within the TME, aptamers could potentially improve treatment outcomes and overcome the challenges associated with larger therapies such as antibodies.

Major limitations in the effective treatment of neurological cancer include systemic cytotoxicity of chemotherapy, inaccessibility, and inoperability. The capability to successfully target a drug to the tumor site(s), without incurring serious side effects, especially in the case of aggressive tumors, such as glioblastoma and neuroblastoma, would represent a significant breakthrough in therapy. Orthotopic systems, capable of storing and releasing proteins over a prolonged period at the site of a tumor, utilising nanoparticles, liposomes, and hydrogels have been proposed. One candidate for drug delivery is Micro-Fragmented Adipose Tissue (MFAT). Obtained easily from the patient by abdominal subcutaneous liposuction (autologous), and with a high content of Mesenchymal Stem Cells (MSC), mechanically derived nanofat is a natural tissue graft with a structural scaffold organization. It has a well preserved stromal vascular fraction, and a prolonged capacity to secrete anti-tumorigenic concentrations of pre-absorbed chemotherapeutics within extracellular vesicles. This review discusses current evidence supporting the potential of drug modified MFAT for the treatment of neurological cancer with respect to recent preclinical and in vitro studies. Possible limitations and future perspectives are considered.

The CRISPR/Cas9 gene editing system has enormous potential in the treatment of multiple genetic disorders. To fully harness this potential, it is essential to deliver CRISPR-Cas9 components safely and effectively into the nuclei of target cells. In this study, we tested the amphipathic cell-penetrating peptide LAH5, previously used for DNA delivery, to intracellularly deliver spCas9: sgRNA ribonucleoprotein (RNP) and RNP/single-stranded homology-directed repair (HDR) template. We discovered that the LAH5 peptide effectively formed nanocomplexes with both RNP and RNP/HDR cargo, and that these nanocomplexes were taken up by cells effectively. Peptide/RNP nanocomplexes were characterized for size and charge, and nanocomplexation with RNP and RNP/HDR cargo was demonstrated via an electrophoretic mobility shift assay. Various ratios of peptide/RNP nanocomplexes were functionally screened on fluorescent reporter cell lines for gene editing and HDR-mediated gene correction. Additionally, targeted gene editing of the CCR5 gene was demonstrated in various cell lines. This LAH5-based delivery strategy paves the way for the development of therapeutic delivery systems for CRISPR/Cas-based genomic engineering.

Erectile dysfunction (ED) is a common and feared complication of radical prostatectomy (RP) for prostate cancer. Recently, tissue engineering is being attempted for post-prostatectomy ED, with controlled interactions between cells, growth factors, and extracellular matrix (ECM) being important for nerve regeneration's structural integrity. In this study, we evaluated the effects of biomechanical ECM patch on human bone marrow-derived mesenchymal stem cells (hBMSCs) morphology and behavior in bilateral cavernous nerve injury (BCNI) rat model. The ECM patch, made of decellularized human fibroblast-derived ECM (hFDM) and a biocompatible polyvinyl alcohol (PVA) hydrogel, was tested with human bone marrow-derived mesenchymal stem cells (hBMSCs) on a bilateral cavernous nerve injury (BCNI) rat model. In vitro analysis showed that the hFDM/PVA + hBMSCs patches significantly increased neural development markers. In vivo experiments demonstrated that the rats treated with the hFDM/PVA patch had higher ICP/MAP ratio, a higher ratio of smooth muscle to collagen, increased content of nNOS, higher levels of eNOS protein expression, and a higher cGMP level compared to the BCNI group. These results indicate that the hFDM/PVA patch is effective in promoting angiogenesis, smooth muscle regeneration, and nitrergic nerve regeneration, which could contribute to improved erectile function in post-prostatectomy ED.

Cancer is one of the leading causes of death, and latest predictions indicate that cancer- related deaths will increase over the next few decades. Despite significant advances in conventional therapies, treatments remain far from ideal due to limitations such as lack of selectivity, non-specific distribution, and multidrug resistance. Current research is focusing on the development of several strategies to improve the efficiency of chemotherapeutic agents and, as a result, overcome the conventional therapies challenges. In this regard, combined therapy with natural compounds and other therapeutic agents, such as chemotherapeutics or nucleic acids, has recently emerged as a new strategy for tackling the drawbacks of conventional therapies. Taking this strategy into consideration, the co-delivery of the above-mentioned agents in lipid-based nanocarriers provide some advantages by improving the potential of the therapeutic agents carried. This review encompassed different strategies associated with combined therapy, at the same time highlighting the most recent advances and outstanding advantages of lipid-based nanocarriers for achieving a promising combination therapy that may overcome cancer treatment challenges.

Given the recent emergence of Rift Valley Fever (RVF) in Rwanda and its profound impact on livelihoods and health, improving RVF prevention and control strategies is crucial. Vaccinating livestock is one of the most sustainable strategies to mitigate the impact of RVF on health and livelihoods, yet vaccine supply chain constraints severely limit the effectiveness of vaccination programs. In the human health sector, unmanned aerial vehicles, i.e., drones, are increasingly being used to improve supply chains and last-mile vaccine delivery. We investigated perceptions on whether delivering RVF vaccines by drone in Rwanda might help to overcome logistical constraints in the vaccine supply chain. We conducted semi-structured interviews with stakeholders in the animal health sector and Zipline employees in Nyagatare District in the Eastern Province of Rwanda and used content analysis to identify key themes. We found that stakeholders in the animal health sector and Zipline employees believe that drones could improve RVF vaccination in Nyagatare. The main benefits study participants identified included decreased transportation time, improved cold chain maintenance, and cost savings.

Background Nitrous Oxide (N₂O) is a dissociative anaesthetic that is sometimes used recreationally. The prevalence of N₂O use is difficult to quantify but appears to be increasing. Research on N₂O harms and application of harm reduction strategies are limited. The aim of this mixed method systematic review was to collate and synthesise the disparate body of research on recreational nitrous oxide use to inform harm reduction approaches tailored for young people. Methods To identify publications reporting recreational use of N₂O, a search of public health, psychology and social science databases was conducted. Databases included PubMed, CIHNAL, PsycINFO, Scopus and Web of Science. Gray literature and Google advanced search were also used. Due to limited published literature on the recreational use of N₂O, no limit was placed on publication date or study type. A thematic synthesis extracted descriptive and analytical themes from the selected studies. Quality appraisal was conducted using the CASP Tool for Qualitative studies and the Joanna Briggs Institute case report assessment tool Results The search retrieved 407 reports. Thirty-four were included in the final analysis including sixteen case reports. The included studies were primarily concerned with raising awareness of the apparently increasing use and subsequently increasing harms of recreational N₂O use. There was limited reference to policy or legislative responses in any published studies, no suggestions for harm reduction strategies or application of service level responses. In general, individuals lack awareness of N2O related harms. Conclusion The review found three key areas that deserve further consideration including: 1) policy, 2) service delivery, and 3) harm associated with N₂O use. We recommend a top-down (policy) and bottom-up (services delivery/services users) approach to harm reduction for N₂O use which also includes further consultation and research with both groups. Future research could explore young people’s experience of N₂O use including benefits and problems to inform contextually relevant harm reduction strategies.