Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.

The rapid convergence of Artificial General Intelligence (AGI), autonomous drones, and applied robotics presents a transformative opportunity for many sectors. However, this advancement also raises critical ethical and existential questions, particularly in warfare. This paper explores the concept of entropy as a metaphor for the potential disorder introduced by these increasingly complex technologies. We examine the risks of AGI surpassing human control in conflict situations, where autonomous decision-making could have disastrous consequences. We then analyze autonomous drones, scrutinizing their impact on warfare tactics and the ethical dilemmas surrounding independent, real-time decision-making. Finally, we investigate applied robotics in military operations, focusing on the delicate balance between enhanced capabilities and the potential for uncontrollable systems. Through a multidisciplinary lens, drawing on technology ethics, military strategy, and AI safety, this paper utilizes the concept of entropy to highlight the need for caution in developing these technologies. We propose a scientifically grounded and ethically sound framework to guide policymakers, technologists, and ethicists in navigating the path between innovation and global stability. This framework concludes with recommendations for responsible development and deployment strategies that can mitigate the risks associated with these powerful tools.

The increasing demand for higher power in rocket launchers is driving the development of higher power nozzles, achieved essentially by increasing the expansion ratio. However, this can lead to flow separation and resulting unsteady, asymmetrical forces, called side loads, which can limit the life of both the nozzle itself and other engine components. If this problem can be overcome, engine performance can be significantly increased. Therefore, various separation control methods have been proposed, but none have been fully implemented to date due to the uncertainties associated with modeling and predicting the flow phenomena. A numerical study of high area ratio rocket engine is presented to analyze the aeroelastic performance of the structure under the condition of flow separation. The finite volume method, the 2nd order upwind scheme and the extended wall function are used to analyze the flow inside the rocket nozzle and the transition of the Free Shock Separation (FSS) to Restricted Shock Separation (RSS) separation pattern ) to be discussed in detail. Since the location of the flow separation point depends heavily on the flow.

The Circular Bioeconomy (CBE) combines the concepts of bioeconomy and circular economy. As an alternative concept to the current fossil-based, linear economy, it de-scribes an economy based on the efficient valorization of biomass. It is regional in nature and aims to improve sustainability. An analysis of the transition process, by identifying its success criteria and assessing its impacts through the modelling of technology-specific scenarios is necessary to ensure that CBE concepts are sustainable. However, a compre-hensive consideration of regional influences on both is lacking. Based on extensive literature research and an expert survey, we (i) present a compre-hensive catalog of CBE success criteria and discuss their region-specific character and (ii) develop a methodology based on evaluation matrices that enable to match CBE technolo-gies with regions. The matrices support the evaluation of technological and regional characteristics influencing the successful CBE implementation. The results show that the success criteria "biomass resources", "technological", and "social" are perceived as highly important, and that most of the success criteria are both region- and technology-specific, highlighting the relevance of developing matrices to match them. We describe such matrices indicatively for the two broadest and most im-portant success criteria clusters “social acceptance” and “biomass supply chain”. With this, we substantiate the regional nature of CBE and raise the awareness on the importance of considering regional conditions in CBE transition processes. Furthermore, we provide practical guidance on how regional conditions can be reflected in the selection of technologies, e.g. in regional CBE technology scenarios.

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silencing a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1-4) peptides. The peptide:siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide:siRNA complexes showed serum stability at N/P ≥40. The synthesized conjugates, with a diameter of <100 nm, formed nano complexes with siRNA and exhibited stable range of zeta potential values (13-18 mV at N/P 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of successful cellular internalization of siRNA. Peptides oleyl-(WRH)3 and oleyl-(WRH)4 showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)4 demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells.

This paper presents MADS (Multi-Agents for Data Science), an innovative and simple open-source multi-agent framework designed for systemic pipeline execution in applied supervised machine learning. By leveraging the capabilities of multi-agent systems (MAS), we introduce a universal approach to optimize and streamline machine learning pipelines. Our framework highlights the differences between various types of agents, such as reinforcement learning (RL) agents and large language model (LLM) agents, and their distinct contributions to the process. While we currently employ LLM agents to automate and enhance machine learning tasks, we acknowledge the potential of incorporating RL agents in future iterations to further improve performance and adaptability. The primary objective is to enhance the efficiency, scalability, and adaptability of supervised learning applications across various domains. This integration addresses the complexity and manual effort typically associated with machine learning workflows, paving the way for more automated, robust, and scalable solutions. Our approach demonstrates significant improvements in task automation, reduced human intervention, and enhanced model performance. The MADS framework, which will soon be available as an open-source implementation, represents a pivotal contribution to the field of machine learning, promising to facilitate broader adoption and collaborative advancement.

The paper presents a proposal for an in-house mathematical model of a liquid flat-plate solar collector. The proposed model is a one-dimensional distributed parameter model enabling simulations of the collector operation under arbitrarily variable boundary conditions. The model is based on the solution of energy balance equations for all components of the collector. The formulated differential equations are solved iteratively using an implicit difference scheme. In order to obtain a stable numerical solution, it is necessary to use appropriate steps of the time and spatial division. These were found by comparing the results obtained from the model with the results of the analytical solution available in the literature for the transient state, which constitutes the novelty of the present study. The accuracy of the results obtained from the model was verified experimentally by comparing the measured and the calculated history of the fluid temperature at the outlet of the collector. The calculation of the collector time constant is proposed in the paper as an example of the model practical application. The results of the time constant calculation were compared with the values obtained experimentally on the test stand. This is another novelty of the presented research. The analysed collector instantaneous efficiency was then calculated for selected outdoor conditions. The presented mathematical model can also be used to verify the correctness of the collector operation. Comparing, on an ongoing basis, the measured and the calculated values of the fluid temperature at the collector outlet, conclusions can be drawn about the process of solar glass fouling or glycol gelling. The model's simplicity and the low computational demands enable such comparisons in an online mode.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

Background/Objectives: Forceps delivery is a crucial obstetrical technique that has been increasingly underutilized in favor of cesarean delivery, despite numerous complications related to cesarean section. The major concerns in assisted vaginal birth (AVB) are the safety and long-term consequences. Thus, we aimed to investigate the neurodevelopmental outcome of children born with forceps delivery up to the age of seven. Methods: A prospective descriptive study was conducted from January 2011 to December 2016 among 49 women from our department in the Clinic for Gynecology and Obstetrics, University Clinical Center of Serbia. The study included women with term singleton cephalic pregnancies. Descriptive statistics were calculated for the baseline demographic and clinical features, whereas the logistic regression analysis was used to explore the association between various perinatal parameters and neurological status of newborns. The Sarnat and Sarnat classification was used to evaluate neurological status of newborns, while long-term neurodevelopmental outcome was assesed with Griffiths Mental Development Scale and additional questions based on the neurologist's clinical practice and experience. Results: Pathological neurological status of the newborn was found in 16.3%, with pathological ultrasound of CNS in 3%. A statistically significant association was observed with Apgar score, odds ratio of 0.575 (95% CI: 0.407–0.813, p = 0.002) and perinatal asphyxia, odds ratio of 9.882 (95% CI: 1.111–87.902, p = 0.04). However, this was unlikely to be related to the mode of delivery. Long-term adverse neurological outcome was seen in three cases, which accounts for 6.4%. These included mild disorders, such as delayed milestone, speech delay and motor clumsiness. Conclusion: The present study highlights the safety of forceps delivery regarding children's neurological outcomes at 7 years of age. This is an important contribution to the modern management of labor, especially in light of increasing rates of cesarean deliveries worldwide.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nano-delivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nano-encapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nano-encapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nano-encapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes.

Public restrooms are often a hub of microbial contamination, and the examination of bacterial contamination in these facilities can serve as an important indicator of the transmission of infectious diseases. This study was conducted to determine the prevalence of bacterial contamination in public restrooms based on the economic class of the building. Samples were collected from various spots in 32 restrooms found in 10 shopping malls, classifying them into two categories: upper-end restrooms and lower-end restrooms. The findings showed that the level of contamination was higher in the lower-end restrooms, with the seat being the most contaminated area. The most dominant Gram-positive bacteria were coagulase-negative staphylococci species, making up 86% of the identified Gram-positive isolates. The most dominant Gram-negative bacteria identified were Klebsiella pneumoniae and Pseudomonas aeruginosa. The antibiotic sensitivity test results revealed the presence of multi-drug resistant bacteria among the Gram-positive and negative isolates, including Staphylococcus haemolyticus, Staphylococcus kloosi, Acinetobacter baumanii, and Pseudomonas aeruginosa. In conclusion, the study underscores the significance of monitoring bacterial contamination in public restrooms and the need for measures to reduce the spread of infectious diseases. Further research is crucial to gain a complete understanding of the bacterial contamination in public restrooms and their resistance patterns, to ensure the safety and health of the public. The implementation of improved cleaning practices and hands-free designs in restrooms can help reduce the risk of cross-contamination and prevent the spread of diseases.

In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

The utilization of electroporation for delivering the CRISPR/Cas9 system components has enabled efficient gene editing in mammalian zygotes, facilitating the development of genome-edited animals. In our study，This research focused on targeting the ACTG1 and MSTN genes in sheep, revealing a threshold phenomenon in electroporation with a voltage tolerance in sheep in vitro fertilization (IVF) zygotes. Various poring voltages near 40V and pulse durations were examined for electroporating sheep zygotes. The study concluded that stronger electric fields required shorter pulse durations to achieve the optimal conditions for high gene mutation rates and reasonable blastocyst development. The investigation also assessed the quality of Cas9/sgRNA ribonucleoprotein complexes (Cas9 RNPs) and their influence on genome editing efficiency in sheep early embryos. It was highlighted that pre-complexation of Cas9 proteins with single-guide RNA (sgRNA) before electroporation was essential for achieving a high mutation rate. The use of suitable electroporation parameters for sheep IVF zygotes led to significantly high mutation rates and heterozygote ratios. By delivering Cas9 RNPs and single-stranded oligodeoxynucleotides (ssODNs) to zygotes through electroporation, targeting the MSTN (Myostatin) gene, a knock-in efficiency of 26% was achieved. The successful generation of MSTN-modified lambs was demonstrated by delivering Cas9 RNPs into IVF zygotes via electroporation.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.

Background: The last-mile delivery phase, the final stage where goods move from a distribution center to customers, is pivotal but faces significant inefficiencies and high costs due to its complexity. Recent advancements in Edge AI or Edge Intelligence (EI) offer promising solutions to these challenges. Methods: This study explores how AI-driven technologies and real-time data processing, combined with EI, can enhance last-mile delivery operations. A thorough literature review was conducted to assess technological advancements, and a Delphi method was used to systematically and empirically assess the impact of EI solutions on both operational efficiency and customer satisfaction. Results: Although EI technologies offer substantial benefits, EU companies are hesitant to adopt these innovations due to high implementation costs. However, firms that have embraced these technologies report significant improvements, including better route optimization, reduced delivery times, and enhanced service reliability. These findings highlight the need for a culture of innovation and the recruitment of experts with advanced qualifications to drive technological advancement in last-mile logistics. Conclusions: The integration of EI represents a significant step towards more efficient, cost-effective, and customer-focused last-mile delivery solutions. Future research should aim to refine these technologies and explore their long-term impacts on the logistics industry.

The theory of water transport in trees, according to which the main driving force of water movement is the suction created by the evaporation of water by the meniscus (the curved surface of the capillary liquid column) on the evaporating elements, supported from below by root pressure, is flawed. The capillary effect in nature is around one meter. In the case of open-air gaps, the leaf cannot suck in the water against gravity because, in this case, the plant would not be sucking in water, but air through the open-air gap. If not, how do trees transport water? When evaporation occurs, there is no suction towards the canopy, but pressure is due to a reduction in the cross-section of the water pipe caused by heat loss through evaporation. At night, when evaporation stops, a thermal equilibration process is triggered, which restores the original cross-section of the pipe. This generates suction and draws water from the soil. As the hydrostatic pressure in the pipe is high for tall trees, the pipe is cut off. To prove my theory, I have given several examples. Water transport is not based on physical mechanical laws alone. There may be complex physiological, biochemical, and biophysical processes behind the operation of the pipe system.

Cancer, characterized by abnormal cell proliferation driven by genetic mutations, remains a significant health challenge. Tailoring effective therapies depends on factors like tumor location, grade, and stage, alongside patient condition. Leveraging Nano-carrier encapsulated drugs offers a promising avenue, as they accumulate preferentially at tumor sites, enhancing therapeutic efficacy while mitigating side effects. Polymeric Nano-carriers, with their customizable properties, further optimize drug delivery efficiency and specificity. Incorporating active targeting ligands such as antibodies, carbohydrates, peptides, folates, and aptamers-onto polymeric nanoparticle surfaces through techniques like functionalization, adsorption, and conjugation plays a pivotal role in directing therapeutic agents to tumor cells. Consequently, polymeric nanoparticles emerge as the carrier of choice for delivering drugs to various tumor types, including breast, colon, lung, prostate, liver, and spleen tumors.

Mortality rates in sub-Saharan Africa remains unacceptably high, and disproportionately affecting economically disadvantaged communities. And healthcare delivery which is considered a major contributor to this is challenged by the limited resources and high service costs, prompting many patients to opt for outpatient department services. This study addresses the need for a data-driven approach to healthcare policy formulation by proposing a model for the implementation of a data warehousing system that integrates outpatients into the national healthcare framework. By leveraging data warehousing, healthcare delivery can be made more efficient through a robust repository that supports decision-making and policy formulation. The research focuses on the outpatient department in resource-scarce settings, proposing a novel multidimensional data model and practical framework implementation. The benefits include improved patient experiences, cost-effective service delivery, and enhanced patient management through electronic health records. Additionally, mobile apps are explored for patient navigation and reminders to enhance treatment adherence. The study’s results indicate that data warehousing can significantly improve healthcare delivery by consolidating critical data and facilitating better planning, resource allocation, and policy formulation. Ultimately, this approach offers valuable insights for optimizing healthcare systems in resource-constrained environments, enabling data-driven policies, and improving health outcomes across sub-Saharan Africa.

Toll plaza optimization is essential for improving traffic flow and easing congestion on road networks. This study aims to suggest and assess potential optimization solutions for the Peshawar toll plaza, considering variables like traffic volume, toll-collecting effectiveness, and customer facilitation. Different resources are used for data collection, like the National Highway Authority of Pakistan. Physical data is collected from the established Toll Plaza of Peshawar, along with the development of each line. The goal of this study is to suggest and assess potential optimization solutions for the Peshawar toll plaza, considering variables like traffic volume, toll-collecting effectiveness, and customer happiness. The analysis of present traffic patterns, the detection of bottlenecks, and the creation of plans to ease congestion and enhance overall traffic flow are all part of the optimization process. The approaches used in this study include data analysis, simulation, and traffic modeling. PTV VISSIM is software for transportation planning, design, and analysis. The simulations consider various conditions, such as variable traffic volumes, toll collection methods, and lane configurations. When comparing the different optimization strategies, performance indicators like trip time, latency, and queue length are utilized to determine which approach is practical. Waiting time Vs. Existing each lane, etc, is explained. In the end, comparing queue lengths and throughput across different lane scenarios shows that maximizing throughput with existing lanes yields up to 45% improvement with E-tag lanes, 40% with existing E-tag lanes, 38% with E-tag plus additional toll and cash lanes, 32% with three cash lanes, and 28% with two E-tag lanes. Failure to regularly monitor and adjust the existing lane pattern scenario based on traffic patterns can lead to queues being 20% longer. Without proactive evaluation and optimization, there is a potential 63% opportunity for queue length improvement

Astaxanthin (ATX) is a carotenoid nutraceutical with a poor bioavailability due to its high lipophilicity. We tested a new tailored nano-droplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX, manufactured by Lyotropic Delivery Systems (LDS)), for its capacity to improve ATX pharmacokinetic profile and anti-oxidant efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to compare the pharmacokinetic profile of ATX and LDS-ATX and protein carbonylation and lipid peroxidation assays to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage. Our results show that only LPS-induced oxidative damage was corrected by ATX and LDS-ATX. While in the liver and muscle LDS-ATX was more efficacious than ATX in attenuating oxidative damage to both proteins and lipids, only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. These results strongly suggest improvement of ATX bioavailability and efficacy by the LDS-ATX nano-formulation.

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.

The new unique technology for granulation of metals and nonmetallic melts is presented in the paper. It was created on the newly developed controlled film flow disintegration with rapid cooling of the droplets and solidified granules in amorphous state. Three new phenomena discovered by us created the base for 3 different methods for granulation of metals and nonmetallic melts in a wide range of granules’ sizes. Electromagnetic resonance method allows producing granules of metals in the range of 1 mm and over. The soliton-like vibrational regime is available for production of any granulation material in the range 0.1-1 mm. Moreover, the shockwave regime is applicable for producing particles from 10 micrometers by size. All methods produce particles of the stated size with a narrow distribution by size: deviation from the average size no more than 50%. The other known methods do not produce granules with such high cooling rate, which can realize the amorphous state and cannot regulate size of particles in such bright but narrow range from 10 micrometers to 1-2 mm.

Microneedle technology is a novel platform technology that revolutionizes ocular drug delivery and addresses critical challenges in the treatment of ocular diseases. Routine treatment methods, such as eye drops and intravitreal injections, suffer from low bioavailability and poor patient compliance. So, novel advanced platform technologies are required to overcome these challenges. Microneedle is a minimally invasive and promising alternative technique that helps precisely control drug delivery to targeted tissues and organs. This review investigates the potential impact of microneedle technology for eye care, underscoring recent advancements, underlying mechanisms, and emerging preclinical and clinical uses. Different types of microneedles, including solid, coated, dissolvable, and hollow, have demonstrated their potential and capability to bypass several barriers in the cornea and sclera. This ensures effective drug penetration and delivery. The current innovations in material science and fabrication methods have enhanced the safety and efficacy of microneedles, reducing discomfort and the chances of infections. These microneedle technologies offer sustained and controlled drug delivery, which could improve therapeutic outcomes for various disease conditions like age-related macular degeneration, glaucoma, diabetic neuropathy, etc. In the current review, recent preclinical and clinical studies emphasize microneedle-based ocular drug delivery's feasibility and potential benefits. These include improved pharmacokinetics, reduced dosing frequency, enhanced patient adherence, and, most importantly, microneedles offer versatile platforms for delivering a wide range of small and large molecules and gene therapies. Despite the exciting progress, obstacles such as regulatory barriers, scalability, and long-term biocompatibility persist. It will be essential to tackle these challenges through interdisciplinary research and partnerships to integrate microneedle technology into standard clinical use effectively. Ultimately, microneedle drug delivery offers a revolutionary method that has the potential to significantly enhance the treatment and results of ocular diseases, marking the dawn of a new era in eye care.

The majority of existing numerical simulations of the effect of bridge piers on water movement are based on a limited number of bridge piers at a laboratory scale. Furthermore, some 2D numerical simulations for actual bridge projects have deficiencies, including the use of overly large mesh sizes and an inadequate treatment of bridge piers. In this study, we compare three methods of structural mesh encryption, suspension mesh, and nonstructural mesh based on Delft3D, and apply the optimization scheme to a real bridge project. It is demonstrated that optimal results can be achieved by utilising a grid size comparable to the pier diameter (Dp) in the region away from the piers. In the vicinity of the piers, the grid cell size should be no larger than 1/9 Dp. The suspended grid technique (DD Boundary) can yield results consistent with those obtained using a full-area high-resolution grid, provided that the total number of grids can be reduced and the computational time is considerably reduced. In this study, the unstructured mesh (Deflt3D Flexible Mesh) scheme was unable to capture the oscillations of the wake flow behind the bridge piers. However, the application of the optimized scheme in bridge engineering has demonstrated its practical value. The findings of this study on mesh resolution and suspension mesh scheme can be applied to the Delft3D software and are also useful for other numerical simulation work.

The unique structure of G4.0 PAMAM dendrimers allows the drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin (DOX) were optimized. The physicochemical properties of the system were monitored using DLS, CD, and fluorescence spectroscopy. The QCM-D method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier's surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the ITC isotherm. Fluorescence spectra and release curves identified reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of G4.0-DOX was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is important from a therapeutic point of view.

The integration of diverse distributed generation (DG) units, encompassing both Renewable Energy Sources (RES) and non-RES technologies delves into voltage levels, current distributions, and power flows, aiming to optimize and effectively manage the distribution network. An RES-based DGs such as photovoltaic systems and wind turbines, alongside non-RES units like fuel cells and micro turbines. This study proposes a hybrid approach the Multi-Objective Genetic Algorithm - Grey Wolf Optimizer (MOGA-GWO). By merging the strengths of multi-objective genetic algorithms with the efficiency of the Grey Wolf Optimizer, this advanced algorithm seeks semi-optimal solutions for multi-objective optimization problems. The algorithm aims to improve convergence speed without compromising solution quality, offering a promising solution for optimizing the characteristics of DG and RES integration in distribution networks compared to Cuckoo Search and Simulation Annealing Techniques. Key algorithmic operations include individual representation, initialization, fitness function computation, selection, crossover, mutation, and ending conditions. The DG optimal power flow problem is explored with a focus on minimizing generation costs, improving voltage profiles, minimizing losses, enhancing reliability, integrating renewable energy, reducing environmental impact, managing congestion, and ensuring compliance with operational constraints. Beyond traditional considerations, the study emphasizes neglected objectives and constraints, such as cyber-security concerns, real-time operation, regulatory frameworks, social acceptance, lifecycle environmental impact, grid resilience, data privacy, aging infrastructure compatibility, and economic viability.

Chitosan (CS) nanoparticles are under investigation for a wide range of applications in nanomedicine. The structural, molecular and physicochemical properties of chitosan nanoparticles have a direct bearing on their efficacy in drug conjugation and delivery, gene delivery, and tissue engineering. Herein we report on the structural, morphological and molecular properties of chitosan nanoparticles synthesized using the ionic gelation method with the intended purpose of being used for drug delivery. The chitosan nanoparticles (CS-NPs) were prepared in the 0.25 to 1.0% w/v concentration range, whereas separate samples of the 1.0% w/v CS-NPs were also functionalized with polyethylene oxide (PEO) alone and with a diblock copolymer of PEO and polypropylene glycol (PPG). The average size of the CS-NPs was determined from TEM imaging to be in the range of 11.3 to 14.8 nm. The XRD and TEM analyses show that the CS-NPs have semi-crystalline structure with the degree of crystallinity depending upon the nature of synthesis. Our results show that functionalizing the 1.0% w/v CS-NPs with PEO increases the degree of crystallinity whereas functionalizing with the diblock copolymer PEO - PPG results in a significant increase in their degree crystallinity. The CS/TPP concentration (CS:TPP fixed at 1:1 ratio) had no apparent effect on the degree of crystallinity of the CS-NPs. The results from the FTIR analysis confirm incorporation of TPP with CS in the CS-NPs. Additionally, FTIR analysis shows an enhancement of hydrogen bonding that is consistent with the increase in the degree of crystallinity of the CS-NPs.

The accompanying mechanical behavior during the flow of ore-rock dispersion is an important factor leading to the instability and failure of the orepass in the ore storage section. It is of great significance to accurately understand the instability characteristics of the well wall in the ore section, during the ore drawing process by understanding the flow characteristics and internal mechanical transfer mechanism of ore-rock dispersion. Using the discrete element method to analyze the flow characteristics, contact compactness, stress distribution characteristics and contact force probability distribution of the ore-rock dispersion, it realizes the quantitative characterization of the damage degree of ore-rock flow, and reveals the damage mechanism of mine storage wall. The results show that: (1) The friction between ore-rock particles, between ore-rock and well wall is an important reason for the change of the macroscopic flow form of ore-rock from “one” to “V” type. (2) The compactness and stress concentration of ores are increasing with the increase of storage depth, which is shown that with the increase of storage depth, the greater the probability of well wall instability. (3) The probability distribution of contact force strength between particles decreases exponentially in the whole process of ore drawing, in which the strong chain plays a major role in the stability of the dispersion system. (4) The number of overpressure and the overpressure coefficient can be used to quantitatively characterize the wall damage degree under the action of ore-rock flow. The dynamic side pressure decreases periodically in the form of exponential fluctuations, and the dynamic load formed by the ore-rock flow mainly played a role in the lower area of the ore storage section.

Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood-brain barrier (BBB), which prevents passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of pro-inflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance in KAFAK-treated mice. This study demonstrates KAFAK's ability to cross the blood-brain barrier, to lower pro-inflammatory cytokine levels in vivo, and to restore function after a moderate TBI.

In the process of oil and gas development and production, when the flow rate in the wellbore is large, the materials underground will be eroded, causing the operation to be unable to proceed smoothly and reducing the efficiency of oil and gas production. Therefore, optimizing the anti-erosion coating under high-speed flow conditions in wellbore is a very interesting thing. It can greatly improve operational efficiency. In this paper, laser cladding was used to prepare the new coating used in the PDC drill bit. Then, the effects of tungsten carbide and multi-layer graphene on the microstructure and properties of the tungsten carbide coating were studied. The research results indicate that, for new coatings, 60% tungsten carbide and 0.3% graphene are the optimal ratios. After adding WC, the hardness has significantly improved. However, when the WC content further increases more than 30%, the increase in hardness is relatively small. In addition, when the content of graphene is more than 0.3%, the branched structure became thicker, and not only the segregation of Cr, Si and W became very obvious again, but also the segregation of Fe occurred at the Ni enrichment site. The research results contribute to improving oil and gas production and operational efficiency under high-speed fluid flow conditions in the wellbore.

Classifying network flow subsequences in an Industrial IoT gateway is an effective method for identifying Industrial IoT faults. This paper proposes a subsequence classification algorithm SSGBUL-IKNN based on unsupervised learning encoding to address the problem of low classification accuracy. Firstly, we built a network module based on unsupervised learning to encode the flow sequence of the Industrial IoT gateway. In the encoding module, a subsequence calibration algorithm controls the increasing error during the coding process. Then, the specific fault type is obtained through an improved KNN classification algorithm based on the indication distance source from the integrated coding sequences converted by multi-dimensional network flow sequences. The test result on three Industrial IoT datasets of a sewage treatment plant shows that the accuracy of SSGBUL-IKNN in this paper exceeds 92%, significantly higher than the algorithm DTW and TSF. It reaches the classification requirements of Industrial IoT fault diagnosis.

Urban rail transit hub platform is the most important area for passenger flow distribution. In order to calculate passenger flow volume in platform and evaluate platform service level during rush hours, this paper presents a method for modeling and simulation of passenger flow distribution in platform. Passenger flow distribution model (PFDM) is proposed based on the basic analysis and the superposition principle of passenger flow. Simulation design for PFDM is proposed by Anylogic, which contains simulation process and simulation model. Experiment results show that PFDM and simulation design are effective and accordant with the reality scenario, and the simulation precision is comparatively ideal. This research could provide a beneficial reference for train scheduling and operation management under the viewpoint of traffic safety and service level.

Polysaccharides such as alginate and gellan gum are biocompatible and easily accessible biopolymers with excellent properties to produce microparticles as drug delivery systems. However, the production methods often fail in reproducibility, compromising the translational potential of such systems. In this work, microparticles made from gellan gum and alginate were optimized using the coaxial air flow method, and an inexpensive and reproducible production method. A Design of Experiments was used to identify the main parameters that affect the microparticle’s production and optimization, focusing on the diameter and dispersibility. Airflow was the most significant factor for both parameters. Pump flow affected the diameter, whilst the gellan gum/alginate ratio affected dispersibility. After optimization, microparticle swelling, drug entrapment and release profile were analyzed at two pH, 7.4 and 6.5. Using methylene blue as a model drug, higher encapsulation and swelling indexes were obtained at pH 7.4, whilst a more pronounced release occurred at pH 6.5. The microparticle release profiles were studied by resorting to well-known models, showing a Fickian type release. The developed microparticles show promising results as drug-delivery vehicles for biomedical applications.

The most important plastic resins used for wire coating are Polyvinyl Chloride (PVC), Nylon, Polysulfone and Low-high density polyethylene (LDPE / HDPE). In this article,the coating process is performed using elastic-viscous fluid as a coating material for wire coating in a pressure type coating die. The elastic-viscous fluid is electrically conducted in the presence of an applied magnetic field. The governing non-linear equations are modeled and then solved analytically by utilizing an Adomian decomposition method (ADM). The convergence of the series solution is established. The results are also verified by Optimal Homotopy Asymptotic Method (OHAM). The effect of different emerging parameters such as non-Newtonian parameters α and β, magnetic parameter M and the Brinkman number Br on solutions (velocity and temperature profiles) are discussed through several graphs. Additionally, the current result also compares with the published work already available in the literature.

Biopolymer gels have gained tremendous potential for therapeutic applications due to their biocompatibility, biodegradability, and ability to adsorb and bind biological fluids, making them attractive for drug delivery and therapy. The versatility of biopolymer gels in theranostic backgrounds, with a focus on integrating imaging features and facilitating real-time monitoring of drug delivery. Different methods of delivery are explored imaging agents into biopolymer gels, including encapsulation, surface functionalization, nanoparticle encapsulation and layer-by-layer assembly techniques. Integration of Agents and Real-Time Monitoring Drug Delivery We summarize the synthesis methods, general properties, and mechanisms of biopolymer gels functionality, demonstrating their broad applications as multimodal systems for imaging-based therapeutics. These techniques not only enable multiple imaging but also provide signal enhancement and imaging a targeted facilitates, increasing the diagnostic accuracy and therapeutic efficacy. In addition, current techniques for incorporating imaging agents into biopolymer gels are discussed, and their role in precise drug delivery and monitoring.

Abstract: Due to sever land degradation throughout Ethiopia, the government has been implementing massive soil and water conservation works at the watershed scale since 2010 to conserve soil and water resources. However, most of the rivers in Ethiopia carry huge amount of sediment in rainy season and streams dried up in the dry period. Planned research was conducted on two paired micro-catchments Mt.Yewel with the main objective of evaluating the impact of soil and water conservation measures on base flow modification. Stream flow and rainfall data were collected from 22/11/2020 to 8/11/2022 on both micro-catchments at their outlets and center respectively. Base flow separation was done using Sp. Hydro base flow separation tool and SPSS Ver.21 statistical software was employed for data analysis. Flow duration curve (FDC) for both watersheds were developed. The FDC indicated that the base flow from treated micro-catchment ishigher and sustained in the dry season while it is low and un-sustained in untreated micro-catchment. From statistical analysis, there is a significant difference in base flow enhancement between the treated and untreated micro-catchment (P<0.001). Hence, catchment treatment contributed to improve groundwater recharge and sustain base flow in the dry season by reduce surface runoff during rainy season.

Abstract: Severe land degradation is the principal environmental problem in Ethiopian highlands in the form of soil erosion, and soil fertility loss, which is caused by human intervention for food, shelter, and energy demands. Soil erosion contributes to the loss of precious soil and water resources which are the basis of agricultural production and provide numerous other eco-system services. The Ethiopian highlands are one of the most degraded regions in the world. To combat such problems, the government of Ethiopia has been implementing massive soil and water conservation works at the watershed scale since 2010 to conserve soil and water resources. Mount Yewel is one of the highlands in Northeastern Ethiopia where intensive soil and water conserva-tion has been implemented. Despite the massive investment in soil and water conservation measures, most of the rivers in the highlands of Ethiopia carry huge amounts of sediment with high flood risks in the wet season and streams are dried up in the dry period. Nonetheless, the impact of soil and water conservation measures on flood reduction and dry season flow en-hancement has not yet been quantified and evaluated. This research was then conducted on paired micro-catchments of Mount Yewel with the main objective of evaluating the impact of soil and water conservation measures on base flow modification. Stream flow and rainfall data were col-lected from 22/11/2020 to 8/11/2022 on paired micro-catchments of Mount Yewel at their outlets and centers respectively. Base flow separation was done from the stream hydrograph using Sp. Hydro base flow separation tool and SPSS Ver.21 statistical software were employed for data analysis. Flow duration curves (FDC) for both watersheds were developed to compare the stream flow patterns between treated and untreated micro-catchments of Mount Yewel. The FDC indi-cated that the base flow from treated micro-catchment is higher and sustained in the dry season while it is low and unsustained in untreated micro-catchment. From statistical analysis, there is a significant (P

The e-commerce sector is in a constant state of growth and evolution, particularly within its subdomain of online food delivery. As such, ensuring customer satisfaction is critical for companies working in this field. One way to achieve this is by providing accurate delivery time estimation. While companies can track couriers via GPS, they often lack real-time data on traffic and road conditions, complicating delivery time predictions. To address this, a range of statistical and machine learning techniques are being employed, including neural networks and specialized expert systems, with different degree of success. One issue with neural networks and machine learning models is their heavy dependence on vast, high quality data. To mitigate this issue we propose two Bayesian generalized linear models to predict time of the delivery. Utilizing a linear combination of predictor variables, we generate practical range of outputs with Hamiltonian Monte Carlo sampling method. These models offer a balance of generality and adaptability, allowing for tuning with expert knowledge. They were compared with PSIS-LOO and WAIC criteria. Results show that both models accurately estimated delivery times from the dataset, while maintaining numerical stability. Model with more predictor variables proved to be more accurate.

Tissue engineering has the potential for repairing large bone defects, which impose a heavy financial burden on the public health. However, difficulties with O₂ delivery to the cells residing in the interior of tissue engineering scaffolds make it challenging to grow artificial tissues of clinically-relevant sizes. This study uses image-based simulation in order to provide insight into how to better optimize the scaffold manufacturing parameters, and the culturing conditions, in order to resolve the O₂ bottleneck. To do this, high resolution 3D X-ray images of two common scaffold types (salt leached foam and non-woven fiber mesh) are fed into a Lattice Boltzmann Method fluid dynamics and reactive Lagrangian Scalar Tracking mass transfer solvers. The obtained findings indicate that the scaffolds should have maximal surface area-to-solid volume ratios, for higher chances of the molecular collisions with the cells. Furthermore, the cell culture media should be flown through the scaffold pores as fast as practically possible (without detaching or killing the cells). Finally, we have provided a parametric sweep that maps how the molecular transport within the scaffolds is affected by variations in rates of O₂ consumption by the cells. Ultimately, the results of this study are expected to benefit the computer-assisted design of tissue engineering scaffolds and culturing experiments.

The oscillating heat pipe (OHP) is a new member in the family of heat pipes, and it has great potential applications in energy conservation. However, the fluid flow and heat transfer in the OHP as well as the fundamental effects of inner diameter on them have not been fully understood, which are essential to the design and optimization of the OHP in real applications. Therefore, by combining the high-speed visualization method and infrared thermal imaging technique, the fluid flow and thermal performance in the OHPs with inner diameters of 1, 2 and 3 mm are presented and analyzed. The results indicate that three fluid flow motions, including small oscillation, bulk oscillation and circulation, coexist or, respectively, exist alone with the increasing heating load under different inner diameters, with three flow patterns occurring in the OHPs, viz. bubbly flow, slug flow and annular flow. These fluid flow motions are closely correlated with the heat and mass transfer performance in the OHPs, which can be reflected by the characteristics of infrared thermal images of condensers. The decrease in the inner diameter increases the frictional flow resistance and capillary instability while restricting the nucleate boiling in OHPs, which leads to a smaller proportion of bubbly flow, a larger proportion of short slug flow, a poorer thermal performance, and easier dry-out of working fluid. In addition, when compared with the 2 mm OHP, the increasing role of gravity induces the thermosyphon effect and weakens the 'bubble pumping' action, which results in a little smaller and bigger thermal resistances of 3 mm OHP under small and bulk oscillation of working fluid, respectively.

This paper introduces a three-layer system, proposing a comprehensive model of granular mixture transport over a mobile sloped bed in a steady flow. This system, consisting of the bottom, contact and upper zones, provides complete, continuous sediment velocity and concentration vertical profiles. The model considers gravity’s effect on sediment transport in the bottom (dense) layer, a crucial factor often overlooked in previous studies. The induced movement in the mobile sublayer of the dense layer causes an increase in velocity at the upper boundary of this layer, significantly affecting the vertical distributions of velocity and concentration above this layer. We described the interactions between fractions and an intensive sediment mixing and sorting process in the contact layer. The proposed shear variation, with an increase in its maximum value at the bed, adds to the novelty of our approach. The data sets used for the model’s validation cover various conditions, including slopes, grain diameters, densities and grain mobility conditions, from incipient motion to a fully mobilised bed. This extensive validation process instils confidence in the theoretical description and its applicability to real-world scenarios.

An accurate assessment of the stage-discharge relationship in open channel flows is necessary and important to the design and management of hydraulic structures and engineering in practical hydrosystems such as rivers and streams. While the flow structures and patterns at open channel junctions are interesting and have been widely studied in the literature, this paper focuses further on the effect of flow junctions on stage-discharge relationship at mountain river confluences. In this study, both the flume and physical model experiments are designed and performed carefully to test and analyze the complex flow structures and characteristics at river confluences with different configurations and hydraulic conditions. The impacts of the flow junctions on the traditional stage-discharge relationship are analyzed in this study. The results of this study are discussed in the paper for the understanding of flow structures at flow junctions and the design and management of hydraulic structures in river engineering.

In this work, satellite data from the Clouds and Earth’s Radiant Energy System (CERES) and Moderate Resolution Imaging Spectroradiometer (MODIS) instruments is analyzed to determine how the global absorbed sunlight and global entropy generation rate have changed during the time period from 2002 to 2023. The data is used to test hypotheses derived from the Maximum Power Principle (MPP) and Maximum Entropy Production Principle (MEP) about the evolution of earth’s surface and atmosphere. The results indicate that the amount of absorbed sunlight has increased over the last 20 years but rising surface temperatures have caused the entropy generation rate to remain approximately constant despite that decrease in albedo. The results are simpler to explain using the MPP but do not completely rule out the MEP. Given the acceptance of the MPP or MEP, some extensions and nuances are discussed.

This paper proposed three-dimensional numerical simulation method by coupling of electrostatic and fluid fields to evaluating the performance of electrical sensor in the concentration measurement of gas/solid two-phase flow. Compared with the static numerical simulation, this real-time dynamic 3-D simulation method can research on a designed capacitance sensor combining the dynamic characteristics of the two-phase flows for concentration measurement. Several fluid-electrostatic models of transmission pipes with different sensor structures are built. Under different test positions and different particle concentrations, the flow characteristics and the corresponding electric signals can be obtained, and the correlation coefficient between the concentration values and the capacitance values are used for performance evaluation of the sensors. The effects of flow regimes on concentration measurement are also been investigated in this paper. To validate the results of simulation, an experimental platform with horizontal straight pipe for phase volume concentration measurement of solid/air two-phase flow is built, and the experimental results agree well with simulation conclusions. The simulation and test results show that the coupling models can give constructive reference opinions for the sensor design and collection of installation position in different transmission pipelines, which are very important for the practical process of pneumatic conveying system.

Hamman’s syndrome is a rare condition that mostly affects young males, often with a predisposition of asthma. It includes the presence of free air in the mediastinum and subcutaneous emfysema with no other underlying cause such as trauma or infection. It occurs spontanously and often in association with prolonged valsalva manouvre. This might explain why there are some cases of Hamman syndrome among young females giving birth. Here we present a case report of a 24-year- old primigravida with Hamman’s syndrome. She presented with symptoms a few hours after an uncomplicated vaginal delivery at 40+1 pregnancy week. The symptoms resolved spontanously after a few days of observation. We also give a systemic review of reported cases since 2000 to provide overview on pathomechanism, symptoms, diagnostics, treatment and management of this condition. Hamman’s syndrome is a rare, usually benign, but potentially serious complication that can occur during the second stage of labour. Diagnostics include inquiring about typical symptoms, clinical examination and chest x-ray or CT scan. Treatment is usually conservative with oxygen, bronchodilators and pain relief. The reccurence rate is low and there is no contraindication to vaginal delivery in future pregnancies. However, it is suggested that physicians and midwives be cautious and consider low threshold for instrumental delivery or caesarean section to avoid excessive valsalva manoeuvre.

Transmembrane transport of small organic and inorganic molecules is one of the cornerstones of cellular metabolism. Among transmembrane transporters, solute carrier (SLC) proteins form the largest, albeit very diverse, superfamily with over 400 members. It has been early on recognized that xenobiotics can directly interact with SLCs and that this interaction can fundamentally determine their efficacy, including bioavailability and intertissue distribution. Apart from the well-established prodrug strategy, the chemical ligation of transporter substrates to nanoparticles of various chemical composition has recently been used as a means to enhance their targeting or absorption. In this review, we summarize efforts in drug design exploiting interactions with specific SLC transporters to optimize their therapeutic effects. Furthermore, we describe current and future challenges as well as new directions for the advanced development of therapeutics that target SLC transporters.

Vascular impairment, muscle atrophy, and cognitive decline are important age-related conditions that have a significant impact on health. Vascular impairment directly disrupts the flow of blood, leading to the decline of muscle mass associated with aging (sarcopenia) and the decline of neuronal functions (neurodegeneration). Our inadequate understanding of the complex relationships between these conditions impedes precise diagnosis and effective treatment. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can enhance therapeutic strategies and lead to better outcomes for patients. Here, we highlight the intricate relationship among vascular dysfunction, degenerative muscle, and cognitive decline, underscoring the need for multidisciplinary approaches to treatment. Progress in this field can result in improved diagnosis, more potent therapeutic options, and enhanced preventative measures, all of which can contribute to an improved quality of life for the aging population.

Iterated games, in which the same economic interaction is repeatedly played between the same agents, are an important framework for understanding the effectiveness of strategic choices over time. To date very little work has applied information theory to the information sets used by agents in order to decide what action to take next in such strategic situations. This article looks at the mutual information between previous game states and an agent's next action by introducing two new classes of games: ’invertible games’ and ‘cyclical games'. By explicitly expanding out the mutual information between past states and the next action we show under what circumstances these expressions can be simplified. These information measures are then applied to the Traveler's Dilemma game and the Prisoner's Dilemma game, the Prisoner's Dilemma being invertible, to illustrate their use. In the Prisoner's Dilemma a novel connection is made between the computational principles of logic gates and both the structure of games and the agents' decision strategies. This approach is applied to the cyclical game Matching Pennies to analyse the foundations of a behavioural ambiguity between two well studied strategies: ‘Tit-for-Tat' and ’Win-Stay, Lose-Switch'.

We construct a Bayesian estimator for the dilution of a wastewater sample. When wastewater is diluted by rainwater an estimate of the level of dilution is required if we are to normalise sample measurements of disease markers such as SARS-CoV-2 RNA. We consider the situation where flow measurements are available, but will regularly be unreliable because of the action of combined sewer outflows (CSOs) and wastewater storage tanks, which divert wastewater away from treatment plants when the flow is excessive. However, we also have proxies for the flow from various chemical markers (e.g.\ phosphate, ammonium, electrical conductivity), whose level per unit of population is fixed. The new flow estimator has multiple advantages compared to existing procedures: credible intervals for the estimates; optimal weighting of the chemical markers; systematic handling of missing and censored values; and model based smoothing without lags.

The current work reveals the fine tuning between stability zones and randomness of Pointwise Stationary Fluid Flow Approximation (PSFFA) model of the non-stationary queueing D/M/1 system. More specifically, this clearly provides more insights into developing a contemporary PSFFA theory that unifies non-stationary queueing theory with chaos theory and fields in both theoretical physics and chaotic systems. This opens new grounds for stability analysis of non-stationary queueing systems.

ω-Transaminases have been immobilized on macrocellular silica monoliths and used as heterogeneous biocatalysts in a continuous flow mode enantioselective transamination reaction. The support was prepared by a sol-gel method based on emulsion templating. The enzyme was immobilized on the structured silica monoliths both by adsorption, and by covalent grafting using amino-functionalized silica monoliths and glutaraldehyde as a coupling agent. A simple reactor set-up based on the use of a heat-shrinkable Teflon tube is presented and successfully used for the continuous flow kinetic resolution of a chiral amine, 4-bromo-α-methylbenzylamine. The porous structure of the supports ensures effective mass transfer and the reactor works in the plug flow regime without preferential flow paths. When immobilized in the monolith and used in the flow reactor, transaminases retain their activity and their enantioselectivity. The solid biocatalyst is also shown to be stable both on stream and during storage. These essential features pave the way to the successful development of an environmentally friendly process for chiral amines production.

(1) Background: Although diagnostic criteria for massive hemorrhage with organ dysfunction such as disseminated intravascular coagulation associated with delivery have been empirically established based on clinical findings, strict logic has yet to be used to establish numerical criteria. (2) Methods: A dataset of 107 deliveries with ≥2,000 g of blood loss, among 13,368 deliveries from nine national perinatal centers in Japan between 2020 and 2023 was obtained. Twenty-three patients had fibrinogen levels &lt;170 mg/dl, which is the initiation of coagulation system failure per our previous reports. Three of these patients had hematuria. We used six machine learning methods to identify the borderline criteria dividing the fibrinogen/fibrin/fibrinogen degradation product (FDP) planes, using 15 coagulation fibrinolytic factors. (3) Results: The boundaries of hematuria development on a two-dimensional plane of fibrinogen and FDP were obtained. If the FDP–fibrinogen/3–60 (mg/dl) value is positive, this indicates hematuria; otherwise, the case is non-hematuria, as demonstrated by the support vector machine method that seemed the most appropriate. (4) Conclusions: The borderline criterion dividing the fibrinogen/FDP plane for patients with hematuria that could be considered organ dysfunction in massive hemorrhage during delivery was obtained using artificial intelligence, and this method seemed to be useful.

Treatment of bladder cancer remains a critical unmet need and requires advanced approaches, particularly the development of local drug delivery systems. The physiology of the urinary bladder causes the main difficulties in the local treatment of bladder cancer: regular voiding prevents the maintenance of optimal concentration of the instilled drugs, while poor permeability of the urothelium limits the penetration of the drugs into the bladder wall. Therefore, much research effort is spent to overcome these hurdles, thereby improving the efficacy of available therapies. The explosive development of nanotechnology, polymer science and related fields has contributed to the emergence of a number of nanostructured vehicles (nano- and micro scale) applicable for intravesical drug delivery. Moreover, the engineering approach has facilitated the design of several macro-sized depot systems (centimeter scale) capable of remaining in the bladder for weeks and months. In this article, the main rationales and strategies for improved intravesical delivery are reviewed. Here, we focused on analysis of colloidal nano- and micro-sized drug carriers, and indwelling macro-scale devices which were evaluated for applicability in local therapy of bladder cancer in vivo.

Enclosed public spaces are the hotspots for airborne disease transmission. To measure and maintain indoor air quality in terms of airborne transmission, an open source, low cost and distributed array of Particulate Matter Sensors has been developed and named as Dynamic Aerosol Transport for Indoor Ventilation or DATIV system. This system can use multiple Particulate Matter Sensors (PMS) simultaneously and can be remotely controlled using a Raspberry Pie based operating system. The data acquisition system can be easily operated using the GUI within any common browser installed on a remote device such as a PC or Smartphone with corresponding IP address. The software architecture and validation measurements are presented together with possible future developments.

Non steady applied magnetic field impact on a liquid metals has good prospects for industry. For a better understanding of heat and mass transfer processes under these circumstances, numerical simulations are needed. A combination of finite elements and volumes methods was used to calculate the flow and solidification of liquid metal under electromagnetic influence. Validation of numerical results was carried out by means of measuring with ultrasound Doppler velocimetry technique, as well as with neutron radiography snapshots of the position and shape of the solid/liquid interface. As a result of the first part of the work, a numerical model of electromagnetic stirring and solidification was developed and validated. This model could be an effective tool for analyzing the electromagnetic stirring during the solidification process. In the second part, the dependences of the velocity pulsation amplitude and the melt velocity maximum value on the magnetic field pulsation frequency are obtained. It was found numerically the ability of the pulsating force action to develop higher values of the liquid metal velocity at a frequency close to the MHD resonance. Obtained characteristics give a more detailed description of the electrically conductive liquid behaviour under action of pulsating traveling magnetic field.

Scedosporium species are human pathogenic fungi, responsible for chronic, localised, and life-threatening disseminated infections in both immunocompetent and immunocompromised individuals. Diagnosis of Scedosporium infections currently relies on non-specific CT, lengthy and insensitive culture from invasive biopsy, and time-consuming histopathology of tissue samples. At present, there are no rapid antigen tests that detect Scedosporium-specific biomarkers. Here we report the development of a rapid (30 min) and sensitive (pmol/L sensitivity) lateral-flow device (LFD) test, incorporating a Scedosporium-specific IgG1 monoclonal antibody (mAb), HG12, which binds to extracellular polysaccharide (EPS) antigens of between ~15 kDa and 250 kDa secreted during hyphal growth of the pathogens. The test is compatible with human serum, and allows the detection of the Scedosporium species most-frequently reported as agents of human disease (Scedosporium apiospermum, Scedosporium aurantiacum, and Scedosporium boydii), with limits of detection (LOD) of the EPS biomarkers in human serum of ~0.81 ng/mL (S. apiospermum), ~0.94 ng/mL (S. aurantiacum), and ~1.95 ng/mL (S. boydii). The Scedosporium-specific LFD (ScedLFD) test therefore provides a potential novel opportunity for the detection of infections caused by different Scedosporium species.

Carbon nanodots (CNDs) have garnered significant attention as viable drug delivery vehicles in recent years, especially in the field of phytomedicine. Although there is much promise for therapeutic applications with phytomedicine, its effectiveness is frequently restricted by its low solubility, stability, and bioavailability. This paper offers a thorough synopsis of the developing field of phytomedicine drug delivery based on CND. It explores CND synthesis processes, surface functionalization strategies, and structural and optical characteristics. Additionally, the advantages and difficulties of phytomedicine are examined, with a focus on the contribution of drug delivery methods to the increased effectiveness of phytomedicine. The applications of CNDs in drug delivery are also included in the review, along with the mechanisms that underlie their improved drug delivery capabilities. Additionally, it looks at controlled release methods, stability augmentation, and phytomedicine loading tactics onto CNDs. The potential of polymeric carbon nanodots in drug delivery is also covered, along with difficulties and prospective directions going forward, such as resolving toxicity and biocompatibility issues. In summary, the present review highlights the encouraging contribution of CNDs to the field of drug delivery, specifically in enhancing the potential of phytomedicine for therapeutic purposes.

Artificial Intelligence (AI) in healthcare has ushered in a revolutionary era by transforming the way we provide care and reduce adverse consequences. This paper explores the field of AI applications in healthcare, including side effect management, streamlined administrative procedures, and customized treatment programs.

Hydrogels, hydrophilic polymeric compounds, have been recently put under investigation as regenerative medicine applications and delivery systems for antineoplastic drugs, particularly chemotherapeutics (anthracyclines, alkylating agents), target drugs (trastuzumab) and immunotherapies. Porosity, conductivity, biodegradability and physical states are some of the peculiarities that render hydrogels suitable for therapies implementation. Chemically-modifying agents and enzymes can be also coupled to hydrogels for pharmacokinetical parameters improvement and side effects avoidance. Cardiotoxicity is in fact one of the major issues for oncological patients after treatment efficacy. Heart failure, myocarditis and hypertension are causes of morbidity and mortality that can possibly be avoided. Specific reaching of the target tumor site has been achieved by several authors in preclinical in vivo studies but clinical studies are currently under design processes. Polydioxanone, a hydrogel-mimicking agent, is capable to interact with the elastic properties of pulmonary artery. An advantageous characteristic is that can be also reabsorbed within biological systems and can cause a remodeling process of the vessel wall. Hydrogels currently represent a strong topic of interest for researchers and probably will guide future clinical investigations and practice.

The similarities between exosomes and liposomes, together with the high organotropism of several types of exosomes, have recently prompted the development of engineered-exosomes or exosome-mimetics, which may be artificial (liposomal) or cell-derived vesicles, as advanced platforms for targeted drug delivery. Here we provide the current state-of-the-art of using exosome or exosome-inspired systems for drug delivery. We review the various approaches investigated and the shortcomings of each approach. Finally the challenges identified up-to-date in this field are summarized.

Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

This study introduces and demonstrates a comprehensive, accurate, unbiased approach to robust quantitative comparison of Electronic Nicotine Delivery Systems (ENDS) appropriate for establishing substantial equivalence (or lack thereof) between tobacco products. The approach is demonstrated across a family of thirteen pen- and pod-style ENDS products. Methods employed consist of formulating a robust emissions surface regression model, quantifying the empirical accuracy of the model as applied to each product, evaluating relationships between product design characteristics and maximum emissions characteristics, and presenting results in formats useful to researchers, regulators, and consumers. Results provide a response surface to characterize emissions (total particulate matter and constituents thereof) from each ENDS appropriate for use in a computer model and for conducting quantitative exposure comparisons between products. Results demonstrate that emissions vary as a function of puff duration, flow rate, E-Liquid composition, and device operating power. Further, results indicate that regulating design characteristics of ENDS devices and consumables may not achieve desired public health outcomes; it is more effective to regulate maximum permissible emissions directly. Three emissions outcome measures (yield per puff, mass concentration and constituent mass ratio) are recommended for adoption as standard quantities for reporting by manufacturers and research laboratories. The approach provides a means of (a) quantifying and comparing maximal emissions from ENDS products spanning their entire operating envelope, (b) comparative evaluation of ENDS devices and consumable design characteristics, and (c) establishing comparative equivalence of maximal emissions from ENDS. A consumer-oriented product emissions dashboard is proposed for comparative evaluation of ENDS exposure potential. Maximum achievable power dissipated in the coil of ENDS is identified as a potentially effective regulatory parameter.

Background: Early postoperative airway management after laryngo-tracheal surgery is crucial. Acute respiratory failure due to glottis’ oedema may occur, requiring reintubation. This can prolong ventilatory assistance, jeopardizing the anastomosis. To date, only judicious steroid administration and fluid management are available to avoid more invasive procedures. High-Flow-Oxygen-Therapy(HFOT) is a noninvasive O2 support method providing humidification, warmed air, Positive-End-Expiratory-Pressure(AIRVO2). No data exist about HFOT use to prevent early complications after laryngo-tracheal surgery. Methods: Between Sept.2020-Sept.2022, 107 consecutive patients underwent laryngo-tracheal surgery received HFOT(Group A). Data and long-term results were compared with those of 80 patients operated between Sept.2018-Aug.2020(Group B), when HFOT was not available. All patients were operated in a single center. No pre- or post-operative settings changed, except for HFOT introduction. We analyzed and compared the risk for “delayed” reintubation (unexpected reintubation within the first 24-48 hours after extubating/laryngeal mask removal) in the two groups. Results: No patients reported HFOT-related adverse events. Control group(B) presented “delayed” reintubation in 37% (p= 0.027), Intensive Care Unit admission in 67%(p=0.005) and longer hospital stay(p=0.001) compared to HFOT group(A). Minor complications rate was 3% in both group and overall mortality was 0%. Re-stenosis was described in 4.6% of HFOT group, without a statistically significant difference (p=0.7006). Conclusions: Our study is the first to investigate HFOT use in patients undergoing laryngo-tracheal surgery, potentially representing a consistent innovation in the peri-operative management of these patients. With the limit of a retrospective series, we would suggest HFOT use for preventing post-operative reintubation rate, possibly reducing ICU admission and hospital stay.

Polymeric based nanoparticles are garnering significant interest for their potential in drug delivery. Specially, nanopolymers that have been functionalized with molecules, such as proteins or peptides, are a versatile vehicle for drug delivery. Curcumin (Cur) is one of the most commonly studied anticancer compounds and is widely acknowledged as having positive effects on human health. However, its insolubility and low bio-distribution greatly hinder the exploitation of its beneficial traits. In this study, our team created a nano delivery system which utilized a nanopolymer called PCL-PEG (poly(ε-caprolactone)-poly (ethylene glycol)). This system was functionalized with A6 peptide to enable targeted delivery of Cur. The system was designed with advantageous nanoparticles (NPs), including a stable zeta potential (–32.7), small size (54.3), uniform surface morphology, and high hydrophilicity (13.72°). In addition, targeted delivery systems exhibited high encapsulation efficacy (93 ± 0.89 %), and drug loading (16.7 ± 0.9 %), and were characterized by a slow and gradual release profile with a release of approximately 83.13 ± 0.12%. The MTT assay results showed that the formulation known as Cur-NPs-A6 caused a significant increase in cell death in MDA-MB-231 cancer cells (IC50 = 23.31 ± 0.85 µM). The designed delivery system did not cause any harm to the noncancerous MCF-10A cells (normal group). Furthermore, the results of both the RT-qPCR and invasion assays demonstrated that the designed system was able to effectively activate the apoptosis pathway and inhibit cell invasion. Our findings suggest that the use of the designed smart delivery system, which is functionalized with A6 peptide that has a high affinity for CD44 receptor - known to be upregulated in numerous malignant conditions, could be a highly efficient approach to treating cancer.

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

This paper investigates the impact of debt financing on dividend payments when they face the agency costs of free cash flow. Focusing on a sample of 120 firms listed on the Saudi Stock Exchange during the period 2011-2021. The study found a negative association between agency cost of free cash flow and dividend payment. More importantly, our research highlights the significant role of long-term debt in making more prudent use of free cash flow. The obligation to meet interest and principal payments acts as an incentive for them to steer clear of unprofitable expenses and risky investments. Concurrently, long-term debt imposes restrictive clauses in debt contracts, such as minimum dividend distribution requirements, which further encourage higher dividend payments. Since interest and debt repayments are fixed obligations, using free cash flow for dividend disbursement is considered a more profitable and beneficial approach for shareholders in the context of Saudi Arabia.

Glycerol represents a useful functional component of heat-transfer fluids. Glycerol is known to be triboelectrically active. We report how the flow of glycerol, stopped in a cylindrical coiled pipe, influences horseradish peroxidase (HRP) enzyme. Namely, glycerol flow was pumped through the coil and then stopped. After that, we incubated the 0.1 µM solution of HRP near the side of the coil, and then adsorbed HRP onto mica. This operation markedly increased the HRP aggregation on mica in comparison with the control sample. We explain this phenomenon by the influence of triboelectrically induced electromagnetic fields. Our results can be useful in the development of flow-based systems for biosensors and bioreactors.

We monitored the water quality and hydrological conditions of a horizontal subsurface constructed wetland (HSSF-CW) in Beijing, China, for 2 years. We simulated the area rate constant and the temperature coefficient with the first-order kinetic model. We examined the relationships between the nitrogen (N) removal rate, N load, seasonal variations in the N removal rate, and environmental factors, such as the area rate constant, temperature, and dissolved oxygen (DO). The effluent ammonia (NH₄⁺-N) and nitrate (NO₃⁻-N) concentrations were significantly lower than the influent concentrations (p<0.01, n=38). The NO₃⁻-N load was significantly correlated with the removal rate (R²=0.9566, p<0.01), but the NH^₄+-N load was not correlated with the removal rate (R²=0.0187, p>0.01). The area rate constants of NO₃⁻-N and NH₄⁺-N at 20 °C were 27.01±26.49 and 16.63±10.58 m∙yr⁻¹, respectively. The temperature coefficients for NO₃⁻-N and NH₄⁺-N were estimated at 1.0042 and 0.9604, respectively. The area rate constants for NO₃⁻-N and NH₄⁺-N were not correlated with temperature (p>0.01). The NO₃⁻-N area rate constant was correlated with the corresponding load (R²=0.9625, p<0.01). The NH₄⁺-N area rate was correlated with DO (R²=0.6922, p<0.01), suggesting that the factors that influenced the N removal rate in this wetland met Liebig's law of the minimum.

In today’s fast paced, attention-demanding society, executive functions and attentional resources are often taxed. Individuals need ways to sustain and restore these resources. We first review the concepts of attention and restoration, as instantiated in Attention Restoration Theory (ART). ART emphasizes the role of nature in restoring attention. We then discuss essentials of experiments on the causal influences of nature. Next, we expand the concept of ART to include modern, designed environments. We propose a wider perspective termed attentional ecology, in which attention behavior is viewed within a larger system involving the human and their interactions over time with environmental demands. When the ecology is optimal, mental functioning can be a positive “flow” that is productive, sustainable for the individual, and sometimes creative.

Part II, like Part I, discusses geometry, kinematics and statics in detail without taking into account power losses in meshing. The main goal of Part II, however, is to prove that there are complex and structurally coupled planetary gear systems, i.e. containing a closed circuit in which no circulation of power flow is generated. The power flow analysis is also carried out using the direct method, with a slight modification in the way of writing the equations identifying active and passive gears, i.e. at the same time the directions of power flow on all transmission paths. The analysed planetary gear system (PGS) is characterised by mobility equal to 1, i.e. single degree of freedom (DoF). It consists of three subsystems in the form of the 2KH type planetary units connected in series-parallel, specially selected to demonstrate the thesis of this paper. It consists of three subsystems in the form of single planetary subsystems of the 2KH type connected series-parallel, specially chosen to illustrate the thesis of this paper.

Bacteriophages are viruses obligately infecting bacteria. They constitute the most numerous categories of biological forms populating our biosphere and are highly diverse and capable of infecting almost all bacteria. Phages make use of their host cell molecular machinery to express their own genes as they lack the ability to independently reproduce themselves. The inimitable characteristics of bacteriophages have enabled them to become propitious tools in biotechnology and genetic engineering. Phages show no tropism for mammalian cells but however, can be easily modified to present targeting ligands on their surface as coat protein fusions without any negative impacts on phage structure. These displayed ligands thereupon guide the recognition, interaction, and internalization of the phage into cells wherein efficiency of transfection is directly influenced by the copy number of the ligands used for targeting. Engineered phages are more efficacious for transgene delivery and gene expression in cancer cells when compared to other non-viral gene transfer strategies and are therefore being employed in developing cancer vaccines. The high level of stability as well as resistance of bacteriophages to various environmental conditions have enabled the development of virus-like particles (VLPs) capable of successful deliverance of several therapeutic drug cargos into tumors by selective targeting. Phage display technology has been used in therapy of Alzheimer’s disease and drug delivery into the brain. Exogenous peptides fused into the coat protein of phages enables the display of these peptides on the phage surface to generate combinatorial phage that facilitates their rapid separation using their ability to bind to a specific molecular target. Phage therapy has been shown to be safe in clinical settings when compared to antibiotics as it shows no adverse anaphylaxis nor adverse effects such as the emergence of multi-drug resistant bacteria. This review provides intriguing details of the use of natural and engineered phages in the therapy of diseases such as cancer, bacterial infections, bovine mastitis and dementia in addition to the use of CRISPR-Cas9 technology in generating genetically engineered phages. Further, the use of phage display technology in generating monoclonal antibodies against various human diseases is elucidated.

Polymeric hydrogels are promising polymeric functional materials that have been widely used in the biomedical field as an emerging carrier of various therapeutic agents. Polymeric hydrogels as a carrier of therapeutics can leverage therapeutically beneficial outcomes of drug delivery than systemic chemotherapy and can provide spatial and temporal control over the release of various therapeutic agents. Polymeric hydrogels are cross-linked three-dimensional networks constructed by hydrophilic polymers and they are capable of absorbing and re-taining a large amount of water. Polymeric hydrogels share many physiochemical features with natural tissues due to their water abundance, biomimetic microstructure, and intrinsic flexibility. Polymeric hydrogels have excellent biocompatibility, biodegradability, and lower toxicity. Polymeric hydrogels enhance the convenience and efficiency of drug delivery by assisting in situ gelation and controlling drug release by changing their volume and other properties when it encounters some stimuli (e.g., heat, pH, light, and ultrasound). This review aims to outline the overview of polymeric hydrogels, properties, types, advantage, disadvantages, characteri-zation, and their application with present status and future perspective used for the delivery of therapeutics in pharmaceutical and biomedical sciences.

Melatonin is a hormone used for treating several disorders. However, its oral administration is problematic due to the variable absorption and extensive first-pass metabolism. The topical application of this drug does not present these disadvantages and can be used for therapeutic and skin protection purposes. The adsorption and release of melatonin in the montmorillonite clay was investigated experimentally and theoretically. The drug-clay interaction products were prepared and characterized, showing a modified and improved diffusion and release of melatonin. The crystal structure and spectroscopic properties of melatonin and melatonin-water-mineral materials were studied by molecular modeling, finding that the adsorption of this drug is energetically favourable, and the results were consistent with the experimental data. Ab initio molecular dynamics simulations with the metadynamics methodology showed the release of melatonin from the confined interlayer nanospace of montmorillonite to the liquid bulk water with a 20 kcal/mol free energy barrier.

Annually, an estimated 13-26 million newborns need respiratory support and 2-3 million newborns need extensive resuscitation, defined as chest compression and 100% oxygen with or without epinephrine in the delivery room. Despite such care, there is a high incidence of mortality and short-term neurologic morbidity. The poor prognosis associated with receiving chest compression alone or with medications in the delivery room raises questions as to whether improved cardiopulmonary resuscitation methods specifically tailored to the newborn could improve outcomes. This review discusses the current recommendations, mode of action, different compression to ventilation ratio, continuous chest compression with asynchronous ventilations, chest compression and sustained inflation optimal depth, and oxygen concentration during cardiopulmonary resuscitation.

The injury causes resistance in human gastric cancer (GC). This Adverse Outcome Pathway (AOP) entitled “Increases in cellular reactive oxygen species (ROS) and chronic ROS leading to human treatment-resistant gastric cancer (GC)” consists of molecular initiating event (MIE) as “Increases in cellular ROS” and “Chronic ROS”, followed by series of key events (KEs); “porcupine-induced Wnt secretion and Wnt signaling activation”, “beta-catenin activation”, “epithelial-mesenchymal transition (EMT), and adverse outcome (AO) as “human treatment-resistant GC” in the sequence. ROS has multiple roles in disease such as development and progression of cancer, or apoptotic induction causing anti-tumor effects. In this AOP, we focus on the role of sustained levels of chronic ROS to induce the therapy-resistance in human GC. EMT, which is cellular phenotypic change from epithelial to mesenchymal-like features, demonstrates cancer stem cell (CSC)-like characteristics in human GC. EMT is induced by Wnt/beta-catenin signaling, providing the rationale to have Wnt secretion and beta-catenin activation as KEs in the AOP.

Background: Convectional methods for drug delivery often faces setbacks due to systemic distribution, short half-life and degradation of therapeutics and therefore reduce concentrations of drug available to target tissue. Nanotheranostic provide a novel method for treating and diagnosing diseases Methodology: collection and review of relevant literatureResult: while nanotheranostic offer advantage of personalized medicine and often combines diagnosis and therapy using single molecular approach, nuclear medicine relies on radioactive isotopes to diagnosed and destroys cancer cells. In both cases, nanocarriers such as lipid-based, polymer-based, drug-conjugate, inorganic nanoparticles are used to deliver drugs/probes/isotopes to target site, generating images and thereafter chemotherapy/radiotherapy begins.Conclusion: Nanotheranostic plays important role in diseases diagnostic, therapy, imaging, monitoring of disease progression / response through the use of nanocarriers. This is made possible through nanoparticles/nanocarriers that delivers drug to the target tissues/cells.

Purpose: The ongoing COVID-19 crisis has created the need for social distancing between medical staff and patients, therefore, healthcare robotics is increasingly important as regards infectious control. The purpose of this study was to design and fabricate a remote controlled transport robot that could provide an optimum technology base for developing countries, having dual functions of telepresence and delivery operations inside or outside buildings, is easy to assemble and also easily able to be cleaned using standard chemical agents.Methods: This machine was designed and fabricated to incorporate two main functions; delivery and telepresence. The robot consists of a base frame, DC motors for driving and steering systems, actuator motor for driving wheel elevation, Wi-Fi AP/Repeater, network camera, and a necessary a back-up power system.Results: This robot can be used both indoors and outdoors. It can carry loads of more than 80 kg. The machine can cross obstacles greater than 3 cm. It can be cleaned by disinfectant agents. An actuator motor can lift the driving wheels above the surface to prevent gear damage. Conclusion: This article demonstrates the concept of a healthcare telepresence and delivery robot that can provide distancing during the present COVID-19 crisis, using optimum technology for low and middle-income countries. In the future, the researcher should consider development of the delivery controls, combined with the telepresence system using the internet of things, to improve the navigation system, the manipulator system for supporting multi-floor transportation, and also other multi-functional purposes.

Microfluidic devices which integrate both rapid mixing and liquid jetting for sample delivery are an emerging solution for studying molecular dynamics via X-ray diffraction. Here we use finite element modelling to investigate the efficiency and time-resolution achievable using microfluidic mixers within the parameter range required for producing stable liquid jets. Three-dimensional simulations, validated by experimental data, are used to determine the velocity and concentration distribution within these devices. The results show that by adopting a serpentine geometry, it is possible to induce chaotic mixing, which effectively reduces the time required to achieve a homogeneous mixture for sample delivery. Further, we investigate the effect of flow rate and the mixer microchannel size on the mixing efficiency and minimum time required for complete mixing of the two solutions whilst maintaining a stable jet. In general, we find that the smaller the cross-sectional area of the mixer microchannel, the shorter the time needed to achieve homogeneous mixing for a given flow rate. The results of these simulations will form the basis for optimised designs enabling the study of molecular dynamics occurring on millisecond timescales using integrated mix-and-inject microfluidic devices.

A novel determination method using flow-through cartridge purification and ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) was developed for the identification and quantification of 30 mycotoxins (aflatoxin B1, B2, G1, G2, sterigmatocysin, T-2 toxin, diacetoxyscirpenol, roquefortine C, methylergonovine, ergocornine, lysergol, enniatin A, enniatin A1, enniatin B, enniatin B1, beauvericin, deoxynivalenol, 3-acetylDeoxynivalenol, 15-acetylDeoxynivalenol, patulin, verruculogen, neosolaniol, gliotoxin, HT-2 toxin, wortmannin, zearalenone, α-zearalenol, β-zearalenol, α-zearalanol, and β-zearalanol) in feedstuffs. Mycotoxins were extracted from sample by 0.1% formic acid aqueous solution/acetonitrile (16/84 v/v), then purified by a Cleanert® MC clean-up column. As a result, the pigments and other matrices were efficient removed from the sample extract solution. The purified eluate was collected, then evaporated and redissolved by 0.1% formic acid aqueous solution/acetonitrile (70:30 v/v) for UPLC-MS/MS detection. A BEH Shield RP18 chromatographic column was employed for separation of 30 mycotoxins in a total of 14 min. Multiple-reaction monitoring (MRM) mode was applied for qualitative and quantitative analysis, and matrix calibration curves obtained with the external-standard method was used for quantitation of target analytes. Under optimized conditions, the linearity range was from 2 to 1000 ng/g, and the limit of quantification of the developed method was from 2 to 50 ng/g. The recoveries of 30 mycotoxins spiked in urine samples were from 72.0% to 118.5%, and the relative standard deviation was below 20%. The method was also well approved by certified reference sample, and applied on the real feedstuff samples testing successfully.

The development of new turbomachinery designs requires numerous time-consuming and computationally intensive computational fluid dynamics (CFD) calculations. However, most of the generated high spatial resolution data remains unused at later development steps. That is also the case with automated optimization processes that use only a few integral values to determine objectives and constraints. Therefore the development of a data-driven AI model was initiated to ensure the potential of further use of the CFD data which is also used to train the AI model. The presented method subsequently provides a fast approximation of the 3D flow for new designs. In this paper, the structure of the developed AI model is presented and the approximation quality is analysed using a complex, state-of-the-art compressor test case. It is shown that the AI model can reproduce many characteristics of the 3D flow of new designs, and performance measures such as efficiency can be derived from these flow predictions. In addition, the complex test case revealed that greater design variation reduces the AI approximation quality which can lead to undesirable exploratory behaviour in an optimisation setup. Overall, the test case has shown promising results and has provided hints for further improvements of the AI model.

In this paper, a novel deep learning approach based on conditional FLOW is proposed for sea clutter augmentation. Sea clutter data augmentation is important for testing detection algorithms for maritime remote sensing and surveillance due to the expensive and time-consuming nature of sea clutter data acquisition. While the conventional parametric methods face challenges in finding appropriate distributions and modeling time correlations of the sea clutter data, the proposed deep learning approach, GCC-FLOW , can learn the data distribution from the data without explicitly defining a mathematical model. Furthermore, unlike the existing generative deep learning approaches, the proposed GCC-FLOW is able to synthesize sea clutter data of arbitrary length with the stable autoregressive structure using conditional FLOW . In addition, the proposed algorithm generates sea clutter data not only with the same characteristics of the training data, but also with the interpolated characteristics of different training data by introducing a global condition variable corresponding to the target characteristic such as sea state. Experimental results demonstrate the effectiveness of the proposed GCC-FLOW in generating sea clutter data of arbitrary length under different sea state conditions.

Hydrogels have gained significant attention as vehicles for transdermal delivery systems. These polymeric-structured substances have been implemented in pharmaceutical and cosmetic applications. Many factors are employed in their preparation. Light, pH, temperature and specific molecules ligands are commonly used in the production of hydrogels. The Transdermal delivery system (TDD) is a widely used route, used to deliver actives/drugs via the skin. Hydrogels as a TDD have been shown to be efficient in enhancing the efficacy in delivering the actives and drugs. The aim of this review is to discuss the hydrogels application in both dermatological therapeutic and cosmetic applications, covering the types, and properties of hydrogel polymer networks. Furthermore, this review presents one of the most extensively used polymers (Hyaluronic acid HA) in this field and discusses the properties, preparation methods and applications of HA hydrogel patches as a delivery system, including methods of loading the actives and the releasing of these actives from them.

Sustained-release drug delivery systems have evolved significantly over the years, playing a pivotal role in pharmaceutical research and enhancing patient care [1]. This abstract synthesizes key insights from various references to highlight the noteworthy advancements in this field. Recent research has emphasized the importance of understanding drug properties and their impact on sustained-release system design [2] [9]. These advancements enable tailoring drug delivery to optimize therapeutic outcomes [2] [9]. Incorporating innovative technologies such as nanotechnology [1], biodegradable polymers [3], and matrix systems [4] has led to the development of more efficient and patient-friendly sustained-release systems [1] [3] [4] Moreover, the concept of personalized medicine is gaining prominence [5], opening doors to individualized drug delivery strategies [5]. These strategies promise to enhance treatment efficacy while minimizing adverse effects [5]. Theoretical analyses, as exemplified by Higuchi’s work [6], continue to shape the understanding of sustained-release mechanisms [6]. Furthermore, studies on enteric-coated timed-release tablets [10]. highlight advancements in specific drug formulations to meet patient needs [10]. In conclusion, advancements in sustained-release drug delivery systems reflect a dynamic landscape where drug properties, innovative technologies, and personalized approaches converge to improve patient outcomes and drug therapy [7] [8] [10].

To this day, use of oily eye drops and non-invasive retinal delivery remains a major challenge. Oily eye drops usually cause ocular irritation and interfere with normal function of the eye, while ocular injections for retinal drug delivery cause significant adverse effects and a high burden on the healthcare system. Here the authors report a novel topical Non-Invasive Ocular Delivery Platform (NIODP) through the periorbital skin for high efficiency anterior and posterior ocular delivery in a non-human primate model (NHP). A single dose of about 7mg JV-MD2 (omega-3 DHA) via the NIODP reached the retina at Cmax of 111µg/g and the cornea at Cmax of 66µg/g. NIODP also delivered JV-DE1, an anti-inflammatory agent in development for dry eye diseases, as efficiently as eye drops did to anterior segments of NHP. The topical NIODP seems to transport drug candidates through the cornea pathway to the anterior and via the conjunctiva/sclera pathway to the posterior segments of the eye. The novel NIODP method has the potential to reshape the landscape of ocular drug delivery, especially for oily eye drops and retinal delivery, where the success of treatment lies in the ocular tolerability and bioavailability of drugs in the target tissue.

Transdermal drug delivery (TDD) is one of the key approaches for treating diseases, avoiding first-pass effects, reducing systemic adverse drug reactions and improving patient compliance. Microneedling, iontophoresis, electroporation, laser ablation and ultrasound facilitation are often used to improve the efficiency of TDD. Among them, microneedling is a relatively simple and efficient means of drug delivery. Microneedles usually consist of micron-sized needles (50-900 μm in length) in arrays that can successfully penetrate the stratum corneum and deliver drugs in a minimally invasive manner below the stratum corneum without touching the blood vessels and nerves in the dermis, improving patient compliance. Hydrogel-forming microneedles (HFMNs) are safe, non-toxic, no residual matrix material, high drug loading capacity, controlled drug release and are suitable for long-term, multiple drug delivery. This work reviewed the characteristics of skin structure and transdermal drug delivery; introduced TDD strategies based on hydrogel microneedles; summarised the characteristics of HFMNs TDD systems and the evaluation methods of HFMNs; and the application of HFMNs drug delivery systems in disease treatment. The HFMNs drug delivery system has a wide scope for development, but the translation to clinical application still has more challenges.

Nanotechnology is making significant transformation to our world, especially in healthcare and the treatment of diseases. It is widely used in different medical applications, such as in treatment and detection. Targeting diseased cell with nanomedicines is one of the numerous applications of nanotechnology. Targeted drug delivery systems for delivering various types of drugs to specific sites are such a dynamic area in pharmaceutical biotechnology and nanotechnology. Compared to conventional drugs, nanomedicines have a higher absorption and bioavailability rate, improving efficacy and minimizing side effects. There are several drug delivery systems including metallic nanoparticles, polymers, liposomes, and microspheres, but one of the most important is the niosomes, which are produced by nonionic surfactants. Because of the amphiphilic nature and structure, hydrophilic or hydrophobic drugs can be loaded into niosome structures. Other compounds, including cholesterol, can also be applied to the niosomes' backbone to rigidize the structure. Several variables such as the type of surfactant in niosome production, the preparation method, and the hydration temperature can affect the structure of the niosomes. Nevertheless, in-silico design of drug delivery formulations requires molecular dynamic simulation tools, molecular docking, and ADME (absorption; distribution; excretion; metabolism) properties, which evaluate physicochemical features of formulation and ADME attitudes before synthesis, investigating the interaction between nano-carriers and specific targets. Hence, experimenting in-vitro and in-vivo is essential. In this review, the basic aspects of niosomes are described including their structure, characterization, preparation methods, optimization with in-silico tools, factors affecting their formation, and limitations.

Security is a major topic in recent researchers, and finding new methods deliver was the motivations for this research to emphasize and as an awareness to browsers developers to handle images with more care and to enhance exploit detection technology in the browser, as this paper proves that hackers now can attack users with just an image.

This work deals with the numerical investigation of the delivery of potential therapeutic agents through dentinal discs (i.e. a cylindrical segment of the dentinal tissue) towards the dentin-pulp junction. The aim is to assess the main key features (i.e. molecular size, initial concentration, consumption rate, disc porosity and thickness) that affect the delivery of therapeutic substances to the dental pulp and consequently to define the necessary quantitative and qualitative issues related to a specific agent before its potential application in clinical practice. The CFD code used for the computational study is validated with relevant experimental data obtained using micro Laser Induced Fluorescence (μ-LIF) a non-intrusive optical measuring technique. As the phenomenon is diffusion dominated and strongly dependent on the molecular size, the time needed for the concentration of released molecules to attain a required value can be controlled by their initial concentration. Finally, a model is proposed which, given the maximum acceptable time for the drug concentration to attain a required value at the pulpal side of the tissue along with the aforementioned key design parameters, is able to estimate the initial concentration to be imposed and vice versa.

The integration of Artificial Intelligence (AI) in healthcare has transformed clinical practices by improving the accuracy of diagnosis, optimizing surgical procedures, improving the patient experience, and accelerating drug development. This article provides a comprehensive overview of the many applications of artificial intelligence (AI) across several industries, including fast diagnostics, where ML algorithms greatly enhance the accuracy and velocity of disease diagnosis. State-of-the-art robotic-assisted minimally invasive surgical procedures that shorten patients' hospitalization and improve their chances of recovery, cutting-edge AI applications in healthcare monitoring, and medication development. The article also looks at the primary challenges that AI in healthcare will inevitably encounter, such as differences in product quality, a shortage of skilled workers, privacy and ethical issues, and the need for improved regulatory frameworks. Despite the challenges, AI contributes significant advantages to the healthcare industry, providing novel and remarkable contributions to the efficiency of medical procedures and the progress of medical outcomes. The paper emphasizes the importance of cooperation in overcoming current challenges and enhancing the acceptability of AI technology in clinical settings. This will ensure that AI-driven innovations continue to enhance the standards of patient care.

In marine ecosystems communication among microorganisms is crucial since the distance is significant if considered on a microbial scale. One of the ways used by microorganism cells to reduce this gap is the production of extracellular vesicles. Marine bacteria release extracellular vesicles (EVs), small membrane-bound structures of 50 to 250 nm diameter, into their surrounding environment. The vesicles contain various cellular compounds, including lipids, proteins, nucleic acids, and glycans. EVs may mediate the communication between microorganisms in aquatic environments thus influencing ecosystem function and determining the structure and composition of microbial populations. This review will focus on marine bacterial EVs analysing their structure, composition, functions, and applications.

In the realm of smart transportation and mobility, delivery organizations are continuously refining their strategies, harnessing resources and advanced analytical techniques to streamline operations, aiming to achieve optimal solutions in terms of both efficiency and cost-effectiveness. However, a persistent challenge faced by these delivery companies revolves around the effective assignment of delivery personnel to customer orders, often grappling with suboptimal assignments that lead to inefficiencies and delays. To address this issue, we propose an architecture that uses the Munkres algorithm to optimize the task assignment problem for delivery personnel with pending orders, employing different cost functions obtained with deterministic and machine learning techniques. We compared the performance of linear and polynomial regression methods to construct different cost functions represented by matrices with orders and delivery people information. Subsequently, we applied the Munkres optimization algorithm to solve the assignment problem, which optimally assigns delivery people and orders. The results demonstrate that linear regression, used to estimate distance information, can reduce estimation errors by up to 568.52 km (1.51%) for our dataset compared to other methods. Conversely, polynomial regression proves effective in constructing a superior cost function based on time information, reducing estimation errors by up to 17,143.41 minutes (11.59%) compared to alternative methods. The proposed approach aims to enhance delivery personnel allocation within the delivery sector, optimizing the efficiency of this process.

Transdermal drug delivery systems have become an intriguing research topic in healthcare technology and one of the most frequently developed pharmaceutical products in the global market. In recent years, researchers and pharmaceutical companies have made significant progress in developing new solutions in the field. This study sheds light on current trends, collaboration patterns, research hotspots, and emerging frontiers of transdermal drug delivery. Herein, a bib-liometric and patent analysis of data recovered from Scopus and The Lens databases, respectively, is reported over the last 20 years. From 2000 to 2022, the annual global publications increased from 131 in 2000 to 659 in 2022. Researchers in the United States, China, and India produced the highest number of publications. Likewise, most patent applications have been filed in the USA, China, and Europe. The recovered patents are 7,275, grouped into 2,997 patent families, of which 314 were granted. This study could support the work of decision-makers, scientific managers, or scientists to create new business opportunities or save money, time, and intellectual capital, thus, defining when a research or technology project should be a priority or not.

The concept of targeted drug delivery can be described in terms of the drug’s ability to mimic the other biological objects’ property to localize to target cells or tissues. For example, drug delivery systems based on red blood cells or mimicking some of their useful features, such as long circulation in stealth mode, have been known for decades. On the contrary, therapeutic strategies based on macrophages have gained very limited attention until recently. Here we review two biomimetic strategies associated with macrophages, that can be used to develop new therapeutic modalities: First, the mimicry of certain types of macrophages (i.e., the use of macrophages, including tumor-associated, or macrophage-like particles as a carrier for targeted delivery of therapeutic agents); and Second, the mimicry of ligands, naturally absorbed by macrophages (i.e., the use of therapeutic agents specifically targeted at macrophages). We discuss potential applications of biomimetic systems involving macrophages for the new advancements in treatment of infections, inflammatory diseases, and cancer.

Alberta Cancer Exercise (ACE) is an exercise oncology program that transitioned from in-person to online delivery during COVID-19. The purpose of this work was to understand participants’ experiences in both delivery modes. Specifically, survivors' exercise facilitators and barriers, delivery mode preference, and experience with program elements targeting behaviour change were gathered. A retrospective cohort design using explanatory sequential mixed methods was used. 57 participants completed a survey, and 19 subsequent, optional interviews were conducted. Most participants indicated preferring in-person programs (58%), followed by online (32%), and no preference (10%). There were significantly fewer barriers (i.e., commute time) (p<0.01), but also fewer facilitators (i.e., social support) (p<0.01), to exercising online. Four themes were generated from the qualitative data surrounding participant experiences in both delivery modes. Key differences in barriers and facilitators highlighted a more convenient experience online relative to a more socially supportive environment in-person. For future work that includes solely online, focusing on building social support and a sense of community will be critical to optimizing program benefits. Beyond the COVID-19 pandemic, results of this research will remain relevant as we aim to increase the reach of online exercise oncology programming to more underserved populations of individuals living with cancer.

Caffeine is a naturally occurring alkaloid found in various plants. It acts as a stimulant, antioxidant, anti-inflammatory and even an aid in pain management, and is found in several over-the-counter medications. This naturally derived bioactive compound is the best-known ingredient in coffee and other beverages, such as tea, soft drinks, and energy drinks, and is the most widely consumed substance worldwide. Therefore, it is extremely important to research the effects of this substance on the human body. With this in mind, caffeine and its derivatives have been extensively studied to evaluate its ability to prevent diseases and exert anti-aging and neuroprotective effects. This review is intended to provide an overview of the effects of caffeine on cancer, cardiovascular, immunological, inflammatory, and neurological diseases, among others. The heavily researched area of caffeine in sports will also be discussed. Finally, recent advances in the development of novel formulations, in the form of dietary supplements of caffeine and nanocarriers, to enhance the bioavailability of caffeine and its beneficial effects will be discussed. On the other hand, caffeine may contribute to elevated blood pressure, anemia, and migraine.

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.

A combination of Poloxamer 407 (P407) and hydroxypropyl methylcellulose (HPMC) hydrosols is proposed as an in situ thermo-gelling vehicle for the nasal drug delivery of chlorhexidine-silver nanoparticles conjugates (SN-CX). Varying ratios of P407 and HPMC were applied in the presence and absence of SN-CX in order to optimize the gelation temperature (Tg) to values close to the physiological nasal such (30–34°C). Mechanisms for the observed gelation phenomena were suggested based on viscosimetry, texture analysis, and dynamic light scattering. Tests were carried out for sprayability, washout time, in vitro drug release, ex vivo permeation, and antimicrobial activity. When applied separately, HPMC was found to lower the P407 gelation temperature, whereas SN-CX increased it. However, in the presence of HPMC, SN-CX interfered with the P407 micellar organization in a principally contrasting way, while leading to an even further decrease in Tg. SN-CX-loaded nasal formulation composed of P407 16% and HPMC 0.1% demonstrated a desired gelation at 31.9 °C, good sprayability (52.95% coverage of the anterior nasal cavity), mucoadhesion for 70 min under simulated nasal clearance, expedient release and permeation, and preserved anti-infective activity against seasonal Influenza virus and beta-coronavirus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and other pathogens. Our findings suggest that the current development could be considered a potential formulation of a protective nasal spray against respiratory infections.

In this paper, we aim to present real implementation cases where non-visible elements of environmental impact assessments (EIA), wind flow, are visualized using a 3D digital twin technology. The conventional EIA process serves as a crucial tool in the evaluation of potential environmental impacts prior to the initiation of development projects. This evaluation helps to establish a legal and institutional framework that seeks to minimize the adverse effects on the environment. However, traditional EIA methods present challenges, particularly for non-experts, in comprehending the results of assessments involving non-visible environmental factors such as noise, air quality, and wind flow. These elements are often represented in static images or numerical tables, limiting accurate understanding and engagement. Our proposed method, termed Digital Twin based EIA, addresses these limitations by leveraging digital twin technology. This advanced methodology allows for the visualization of non-visible environmental elements in a spatio-temporal dimension, providing a more interactive and comprehensive user interface/experience for both citizens and stakeholders. In this context, we present a unique case study that focuses on visualizing wind flow using this technology. This paper serves as an example of how digital twin platforms can enhance traditional EIA processes, offering a more immersive and informative experience. The evolution of EIA into the digital realm signifies an important step forward in fostering public understanding and engagement in environmental protection efforts.

The rapid development of new retail and the impact of COVID-19 have catalyzed the blowout growth of community group purchasing. The emergence of community group purchasing collection and delivery points (CGPCDPs) has become a new way to solve the "last mile" problem of new retail delivery. Based on the point of interest (POI) data of CGPCDPs of Nansha District, Guangzhou City, this study uses text analysis, spatial analysis, model analysis, and other methods to analyze the operation mode, spatial distribution, and influencing factors of CGPCDPs. The conclusions are as follows: CGPCDPs initiators are mainly shopkeepers. They depend mainly on wholesale and retail shops. Service targets are mainly urban and rural communities, followed by industrial areas. The distribution of CGPCDPs has apparent spatial differentiation. At the macro scale, it shows the characteristics of "central agglomeration and peripheral dispersion". It is distributed along the "northwest-southeast" direction and presents a "dual-core multi-center" pattern. At meso-micro scale, different built environments in developed areas of cities, villages in the city (ChengZhongCun) and rural areas show distinct distribution patterns. The MGWR regression model has a better fitting effect than OLS and GWR. The main influencing factors are population density, construction land, house price, supporting place, residence density, urban community, and road proximity.

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.