Intravitreal injection is the gold standard therapeutic option for posterior segment pathologies, and long-lasting release is necessary to avoid reinjections. There is no effective intravitreal treatment for glaucoma or other optic neuropathies in daily practice, nor is there a non-invasive method to monitor drug levels in the vitreous. Here we show that a glaucoma treatment combining a hypotensive and neuroprotective intravitreal formulation (IF) of brimonidine-Laponite (BRI/LAP) can be monitored non-invasively using vitreous imaging captured with optical coherence tomography (OCT) over 24 weeks of follow-up. Qualitative and quantitative characterization was achieved by analysing the changes in vitreous (VIT) signal intensity, expressed as a ratio of retinal pigment epithelium (RPE) intensity. Vitreous hyperreflective aggregates mixed in the vitreous and tended to settle on the retinal surface. Relative intensity and aggregate size progressively decreased over 24 weeks in treated rat eyes as the BRI/LAP IF degraded. VIT/RPE relative intensity and total aggregate area correlated with brimonidine levels measured in the eye. The OCT-derived VIT/RPE relative intensity may be a useful and objective marker for non-invasive monitoring of BRI/LAP IF.

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors

An elevated level of endoplasmic reticulum (ER) stress is considered an aggravating factor for inflammatory bowel disease (IBD). To develop an ER stress attenuator that is effective against colitis, 4-phenylbutyric acid (4-PBA), a chemical chaperone that alleviates ER stress, was conjugated with acidic amino acids to yield a 4-PBA-glutamic acid conjugate (PBA-GA) and a 4-PBA-aspartic acid conjugate (PBA-AA). The PBA derivatives were converted to 4-PBA in the cecal contents, where the conversion was greater with PBA-GA. After oral administration of PBA-GA (oral PBA-GA), millimolar levels of PBA were accumulated in the cecum, whereas 4-PBA was not detected in the blood, indicating the targeting of PBA-GA to the large intestine. At concentrations in the cecum achievable by oral PBA-GA, 4-PBA effectively attenuated ER stress in human colon epithelial cells. In 2,4-dinitrobenzenesulfonic acid-induced colitis in rats, oral PBA-GA alleviated the damage and inflammation in the colon. Moreover, oral PBA-GA substantially reduced the elevated levels of ER stress marker proteins in the inflamed colon. Moreover, PBA-GA was as effective as the currently used anti-IBD drug, sulfasalazine. In conclusion, PBA-GA is a colon-targeted prodrug of 4-PBA and is effective against rat colitis probably through the attenuation of ER stress in the inflamed colon.

A lot of previous research have proposed various frameworks and algorithms to optimize routes to reduce the total transportation cost, which accounts for over 70% of overall logistics cost. However, it is very hard to find the cases applied the mathematical models or algorithms to the practical business environment cases, especially daily operating logistics services like convenient stores. Most of previous research have considered the developing an optimal algorithm which can solve the mathematical problem within the practical time while satisfying all constraints such as the capacity of delivery and pick-up, and time windows. For the daily pick-up and delivery service like supporting several convenient stores, it is required to consider the unit transporting container as well as the demand, capacity of trucks, traveling distance and traffic congestion. Especially, the reusable transporting container, trays, should be regarded as the important asset of logistics center. However, if the mathematical model focuses on only satisfying constraints related delivery and not considering the cost of trays, it is often to leave the empty trays on the pick-up points when there is not enough space in the track. In this research, it has been proposed to build the mathematical model for optimizing pick-up and delivery plans by extending the general vehicle routing problem of simultaneous delivery and pickup with time windows while considering left-over cost. With the numerical experiments, it has been proved that the proposed model may reduce the total delivery cost. It may be possible to apply the proposed approach to the various logistics business which uses the reusable transporting container like shipping containers, refrigerating containers, trays, and pallets.

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

Human factors are the most relevant issues contributing to adverse events in obstetrics. Specific training of Crisis Resource Management (CRM) skills (i.e., problem solving and team management, resource allocation, awareness of environment, and dynamic decision-making) are now widespread and are often based on High Fidelity Simulation. In order to be used as a guideline in simulated scenarios, they need to be translated into specific and observable behavioral markers. To this purpose, we developed a set of observable behaviors related to the main elements of CRM in the delivery room. The observational tool was then adopted in a two-days seminar on obstetric hemorrhage where teams working in obstetric wards of six Italian hospitals took part to simulations. The tool was used as guide for the Io and as a peer-to-peer feedback. It was then rated for its usefulness in facilitating the reflection upon one’s own behavior, its ease of use, and its usefulness for the peer-to-peer feedback. The ratings were highly positive, around 4 in a 5-point scale. The CRM observational tool is therefore a useful, quick and easy solution to facilitate the debriefing, the peer-to-peer feedback and, most of all, the transfer of safe behavior from simulation to everyday practice.

Amyloid self-assembled from amyloid peptides βΑ40 or βΑ42 is notorious for its neurotoxic effects in plaque and neurofibrillary tangle formations leading to neuron dysfunction and diseases of cognitive decline (e.g. Alzheimer’s, Parkinson’s and Huntington's disease). This contrasts with so-called functional amyloids which are non-toxic ordered template structures amenable to applications in tissue engineering. Amyloid fibrils of variable morphology including long and hollow fibres and flattened tube and spiral ribbon-like structures have been used in engineering applications in nano-biology. Protein assemblies based on amyloid core structures display diverse biological functionalities could be applied in futuristic self-assembling biomaterials in nano-electronics. These possibilities have revolutionized the development of next generation computers and biosensors, ultracapacitors, memristors, actuators, molecular switches and could also be used to develop artificial synapses. Amyloid fibril assemblies have also been used in photoelectric and photon capture light harvesting technologies and been applied in innovative nano-photoelectronics and photovoltaics. Hybrid Aβ(16–22)-α-synuclein amyloid fibrils also exhibit light-harvesting and electron-transfer properties. Engineered amyloid assemblies are thus facilitating innovative futuristic advances in nano-technology. Furthermore, with a better understanding of amyloid fibril assembly processes it may be possible to develop therapeutic methods that prevent the toxic build up of this polymer in brain tissues that leads to diseases of cognitive decline. With the ever-expanding prevalence of these diseases in the ageing general global population, there certainly is a clear and present need to find a remedy for these debilitating conditions.

.Various synthetic nematicides are currently used effectively in the control of plant parasitic nematodes. However, these nematicides have adverse effects on humans and the environment. Neem oil is eco-friendly alternatives to synthetic nematicides. The effectiveness of repeated neem oil application in suppressing the root-knot nematodes infestation in figs seedlings was therefore examined in this study, both in its natural form (10 ml/L) and in its nano-emulsion form (5 and 7 ml/L). The recorded reduction parameters of M. incognita were J2/250g soil, galls and egg masses / 5g roots of infected fig seedlings were measured at that time, and the effects of these natural additives were compared with the Fosthiazate (Krenkel 75%EC). The impact of such soil amendments on some typical plant parameters, the total microbial count of soil, and the overall enzymatic activity of the fig rhizosphere were also included. Obtained results revealed that the soil population density of root knot nematode suppressed by 80.3% , reduction of nematode egg masses (60.4%) due to the application of nano-emulsion of neem oil (at 7ml/L). Present work recommend the use of nano-emulsion of neem oil as one of the effective and eco-friendly means to reduce the root- knot nematode on fig .

Numerous structures at the nano- and microscale manifest distinctive properties with far-reaching implications across diverse fields, including electronics, electricity, medicine, and surface engi-neering. Established methods such as nanoimprint lithography, photolithography, and self-assembly play crucial roles in the fabrication of nano- and microstructures; however, they exhibit limitations in generating high-aspect-ratio structures when utilizing high-viscosity pho-tocurable resins. In response to this inherent challenge, we propose a highly cost-effective ap-proach facilitating the direct replication of high-aspect-ratio structures, specifically nanowires, through the utilization of anodized aluminum substrates. This study elucidates the streamlined fabrication process for multiscale porous surfaces achieved through the evaporation-induced in-tegration of solid nanowires printed with high-viscosity photocurable resin.

In this paper, an intelligent blind guide system based on 2D LiDAR and RGB-D camera sensing is proposed, and the system is mounted on the smart cane. The intelligent guide system relies on 2D LiDAR, RGB-D camera, IMU, GPS, Jetson nano B01, STM32 and other hardware. The main advantage of the intelligent guide system proposed by us is that the distance between the smart cane and obstacles can be measured by 2D LiDAR based on Cartographer algorithm, thus achieving Simultaneous localization and mapping (SLAM). At the same time, through the improved yolov5 algorithm, pedestrians, vehicles, pedestrian crosswalks, traffic lights, warning posts, stone piers, tactile paving and other objects in front of the visually impaired can be quickly and effectively identified. Laser SLAM and improved yolov5 obstacle identification tests were carried out inside a teaching building on the campus of Hainan Normal University and on a pedestrian crossing on Longkun South Road in Haikou City, Hainan Province. The results show that the intelligent guide system developed by us can drive the wheels and omnidirectional wheels at the bottom of the smart cane, and give the smart cane a self-leading blind guide function like a "guide dog", which can effectively guide the visually impaired to avoid obstacles and reach the predetermined destination, and can quickly and effectively identify the obstacles on the way out. The laser SLAM speed of this system is 25~31FPS, which can realize the short-distance obstacle avoidance and navigation function both in indoor and outdoor envionments. The improved yolov5 helps to identify 86 types of objects, the recognition rate for pedestrian crosswalks and for vehicles are 84.6% and 71.8%, respectively; the overall recognition rate for 86 types of objects is 61.2%, and the obstacle recognition rate of the intelligent guide system is 25-26FPS.

The human body contains 60-70% of water, depending on age. As a body fluid, it is not only a medium in which physical and chemical processes take place, but it is also one of the active mediators. Water is the richest substance with non-covalent hydrogen bonds. Water molecules, by themselves (in vacuum), are diamagnetic, but when organized into clusters, become diamagnetic or paramagnetic. Also, biomolecules (DNA, collagen, clathrin, and other proteins) have non-covalent hydrogen bonds in their structure. The interaction, as well as signal transmission, between water and biomolecules is achieved through the vibrations of covalent and non-covalent hydrogen bonds, which determine the state and dynamics of conformational changes of biomolecules. Disruptive conformational changes of biomolecules, cells, and tissues lead to their dysfunctionality, so they are a frequent cause of many disorders and diseases. For example, the rearrangement of hydrogen bonding due to mitochondrial disease mutation in cytochrome bc1 disturbs heme bH redox potential and spin state. In order to prevent and repair the dysfunctional conformational changes, a liquid substance was developed based on the second derivative of the C₆₀ molecule (SD-C₆₀), which has classical and quantum properties. Characterization of SD-C₆₀ by UV-VIS-NIR, FTIR, TEM, and AFM/MFM was done and it is shown that SD-C₆₀ water layers generate vibrations with near-zero phase dispersion which are transmitted through the Fibonacci’s water chains to biomolecules. In comparison to previously published SD-C₆₀ derivate (3HFWC, size until 10 nm, and 1-5 water layers), improved formulation (3HFWC-W, size 10-25 nm, and 6-9 water layers) showed multiplied cytotoxic activity against melanoma cell lines of different aggressiveness. Apart from this, the mode of action was preserved and based on induction of senescence rather than cell death. Importantly, high selectivity toward malignant phenotype was detected. Observed effects can be ascribed to a machinery of hydrogen bonds, which are generated in SD-C₆₀ and transmitted through water to biomolecules. This approach may open a new field in science and healthcare - a “water-based nanomedicine”.

Poor interlaminar fracture toughness has been a major issue in glass fiber-reinforced epoxy resin (GF/EP) laminate composites. In this paper, soft carboxy-terminated liquid nitrile (CTBN) rubber particles and rigid nano-SiO2 are used to toughen the epoxy resin (EP) matrix to improve the interlayer properties of GF/EP laminate composites. The effects of adding two toughening agents on the mechanical and interlayer properties of GF/EP laminates were studied. The results showed that adding the two kinds of particles improved the mechanical properties of the epoxy matrix. When the additional amount of flexible CTBN rubber particles was 8wt%, and the rigid nano SiO2 was 0.5wt%, the fracture toughness of the matrix resin was increased by 215.8%, and the tensile strength was only decreased by 2.3% compared with the pure epoxy resin. On this basis, the effects of two kinds of particles on the interlayer properties of GF/EP composites were studied. Compared with the unmodified GF/EP laminates, the interlayer shear strength and mode Ⅰ interlayer fracture toughness is significantly improved by toughening agent, and the energy release rate GIC of interlayer shear strength and interlayer fracture toughness is increased by 109.2%, and 86.8%, respectively.

This paper presents results of the magnetic dynamics study (the microwave power absorptions at the fixed frequencies, during magnetic field sweeping) in samples of Y3Fe5O12 single crystals in the form of plates and spheres of various sizes, at frequencies exceeding 30 GHz, in magnetic fields up to 18 kOe, at room temperature and T=77 K. It was found, that in this case, the inhomogeneity’s of the magnetic state manifested itself in the Y3Fe5O12 samples in as 2D local phase separation regions. These 2D phase separation regions formed inside domain walls representing superlattices with size’s 700 – 900 Å. Landau diamagnetism or de Haas van Alphen oscillations observed in the 2D phase separation regions at room temperature and T=77 K, depending on the shape and size of the studied plates and spheres.

In its 8th Malaysia Plan (MP*), the Malaysian government has given nanotechnology development a high priority and has been made a Strategic Research (SR) programme. Consequently, an exhaustive and long-term approach is essential. Additionally, specific laws are required to provide an optimal health and safety environment for workers. Consequently, the current study intends to assist Malaysian policymakers in promoting improved safety, risk assessment, and management for nanotechnology workplaces, as well as drafting a comprehensive policy for the recently released DOSH guideline in 2018. Utilizing a unique methodology, this study evaluated the assessment and management of nanotechnology health and safety risks in Malaysia using the international risk governance council (IRGC) framework. In addition to document analysis, n = 20 semi-structured interviews were conducted with representatives of several nanotechnology platforms to collect data that was then analyzed thematically. The research evaluated current workplace safety regulations and laws. Consequently, we propose a future dynamic strategy for Malaysian nanotechnology with more favourable upgrades supported by increased concentrations in the following areas: I policy creation, ii) comprehensive management system, iii) knowledge transfer, and iv) infrastructure management. In addition, the findings highlight the need of cross-sectional communication in bridging existing gaps. This study laid the groundwork for a more systematic and comprehensive health and safety strategy.

A comparative analysis of the features of UV- stimulated emission (SE) of various types of disorder active materials based on ZnO crystallites for a random laser (RL) was carried out. The superlinear increase in the intensity of the UV photoluminescence (PL) band of polydisperse nano- microcrystalline (PNMC) ZnO powder at a wavelength of λ = 387 nm and some narrowing of its half-width in the range of 20-15 nm with increasing pump intensity indicate random lasing with incoherent feedback (FB). Properties of similar UV PL bands under the same conditions from a thin film containing hexagonal ZnO microdisks, as well as samples of monodisperse ZnO nanopowder indicate stimulated emission with coherent feedback. It is shown that, among the studied materials, the PNMC ZnO powder with crystallites contained nano-grains with is the most suitable for creating a laser with incoherent feedback at room temperature. The dominant factor of UV SE in PNMC ZnO powder is radiation transitions under exciton - exciton scattering conditions. The possible mechanisms of this random emission with the continuous spectrum are discussed. The average optical gain coefficient αg at λ = 387 nm in this RL system is estimated, as αg ~ 150 cm-1.

Biochar is a carbon allotrope obtained by pyrolysis of biomass, usually agro-waste. Owing to the demand for sustainable development, biochar is continuously raising much hope in the scientific community. However, in order to impart it with new properties, its modification is required, either in situ during pyrolysis, or after the carbonization process. Herein, we propose a new direct approach to obtain bimetallic copper/nickel nanoparticle-loaded on olive stone biochar. The bimetallic-coated biochar and the reference materials bare biochar, copper-loaded and nickel-loaded biochar were prepared at 400 °C under a stream of dinitrogen from olive pit powder particles impregnated first with citric acid (CA), and then with copper and nickel nitrates. We have employed citric acid in the process in order to check its effect on the structural and textural properties of biochar supporting the metallic nanoparticles. Surprisingly, citric acid induced the formation of agglomerated or even raspberry-shaped, bimetallic copper/nickel nanoparticles. Large 450-500 nm-sized agglomerates of ~80 nm bimetallic CuNi NPs were noted for B-CA@CuNi. Interestingly, for biochar material prepared with initial Cu/Ni=10 molar ratio (B-CA@CuNi10/1), the bimetallic NPs formed unusual nano-raspberries (1748 nm in size) which are agglomerates of individual 10-20 nm-sized CuNi10/1 nanoparticles. The B-CA@CuNi and reference materials were characterized by Raman spectroscopy, scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and magnetometry. The B-CA@CuNi and B-CA@Ni materials could be attracted efficiently with a magnet, but not B-CA@CuNi10/1 due to a low nickel loading. B-CA@CuNi was tested as a catalyst for the degradation of methyl orange (MO). Discoloration was noted within 10 min, much faster than a similar material prepared in the absence of CA. B-CA@CuNi could be recycled at least 3 times with exhibit as fast discoloration catalysis performance. This paper stresses the important role of citric acid in shaping the bimetallic nanoparticles loaded in situ on biochar during the slow pyrolysis process and to enable faster catalysed discoloration of organic dye solution.

The process of water treatment by nanoparticles is one of the most considerable subjects in the cross-field of hydrodynamics, chemistry and mathematics. This paper is dedicated to the case of the flows that appear when squeezing and stretching a spongy with a mix of water with nanoparticles and contaminants. It is assumed that fluid is homogeneous at the starting moment, the parameters of the nanoparticles and contaminants are known, and there is a constant non-homogeneous magnetic field applied to the system. The flow starts moving when the walls of the channel shift to each other. Exact and numerical solutions of the system of ordinary differential equations are used to receive the results. The article gives an answer to the question about stability of the flow and proposes the technique to evaluate the essential characteristics of the system to achieve the treatment process efficiency. The main result is that the considered system shows excellent treatment properties during some part of squeezing stage. This effect does not appear without magnetic field.

Lamellar eutectic structure of Al_0.7CoCrFeNi high-entropy alloy (HEA) is emerging as a promising candidate for structural applications because of its high strength-ductility combination. The alloy consists of a fine-scale lamellar fcc+B2 microstructure with high flow stresses >1500 MPa under quasi-static conditions. The response to shear loading was not investigated so far. This is the first report on the shear deformation of an eutectic structured HEA and effect of precipitation on shear deformation. The dynamic shear response (DSR) of the eutectic HEA was examined in two microstructural conditions, with and without the presence of L1₂ precipitates. A split-Hopkinson pressure bar (SHPB) was used to compress the hat-shaped specimens to study the local DSR of the alloy. The adiabatic shear bands (ASBs) in two different microstructural conditions were characterized after deformation at dynamic strain rates. The adiabatic shear localization occurs at low strains for the high strength material, and the eutectic microstructure does not delay cracking. The width of ASBs and the extent of plastic deformation around them has been correlated with the rate of straining. Dynamic recrystallization within ASBs and profuse twinning around it was observed. Local mechanical response of individual lamellae before and after shear deformation was examined using nano-indentation.

This paper introduces an innovative nanotechnology-based approach that provides a pathway to enhance the energy release efficiency of nanoenergetic materials (nEMs) by harnessing self-synchronized collective atomic vibrations and phonon wave resonance within the transition domains between nanocomponents, without altering the material composition. The key innovation involves incorporating finely-tuned 2D-ordered linear-chain carbon-based multilayer nano-enhanced interfaces as programmable nanodevices into the transition domains using advanced multistage processing and assembly techniques. These programmable nanodevices enable precise control over self-synchronized collective atomic vibrations and phonon wave propagation, leading to synergistic effects. To activate and optimize these effects, a combination of various methods is employed, including energy-driven initiation of allotropic phase transformations, surface acoustic wave-assisted micro/nano-manipulation, heteroatom doping, directed self-assembly using high-frequency electromagnetic fields, and data-driven inverse design approaches. By leveraging a data-driven inverse design strategy and uncovering hidden structure-property relationships, we maximize energy release efficiency using the carbon nano-materials genome approach derived from multifactorial neural network-based predictive models. This approach not only unlocks new functionalities in nEMs but also improves environmental performance and safety levels. By pioneering transformative pathways for nEMs through harnessing phonon wave resonance in low-dimensional nanocarbon transition interfaces, this research brings significant advancements in the field.

The capacity and the mechanism of the adsorption of aqueous barium (Ba), cobalt (Co), strontium (Sr) and zinc (Zn) by Ecuadorian (NatAllo) and synthetic (SynAllo-1 and SynAllo-2) allophanes were studied as a function of contact time, pH and metal ion concentration using kinetic and equilibrium experiments. The mineralogy, nano-structure and chemical composition of the allophanes were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy and specific surface area analyses. The evolution of adsorption fitted to a pseudo-first-order reaction kinetics, where equilibrium between aqueous metal ions and allophane was reached within < 10 min. The metal ion removal efficiencies varied from 0.7 to 99.7 % at pH 4.0 to 8.5. At equilibrium, the adsorption behavior is better described by the Langmuir model than by the Dubinin-Radushkevich model, yielding sorption capacities of 10.6, 17.2 and 38.6 mg/g for Ba^(2+), 12.4, 19.3 and 29.0 mg/g for HCoO_2^-, 7.2, 15.9 and 34.4 mg/g for Sr^(2+) and 20.9, 26.9 and 36.9 mg/g for Zn^(2+), respectively, by NatAllo, SynAllo-2 and SynAllo-1. The uptake mechanism is based on a physical adsorption process. Allophane holds great potential to remove aqueous metal ions and could be used instead of zeolites, montmorillonite, carbonates and phosphates for wastewater treatment.

Background: The development of new technologies, interpretation of amputations as therapeutic failures by society, and high morbidity and mortality associated with external hemipelvectomies make these mutilating surgical procedures appear obsolete. Herein, we review the scientific literature on the topic and present two cases of high-grade ulcerated soft tissue sarcomas in the gluteal region showing exceptional behavior and different outcomes. Methods: We performed a literature review of the PubMed databases from 2022 to April 2024. Additionally, we present two cases of soft tissue sarcomas in 18- and 71-years old female patients, which were treated with extended external hemipelvectomies with anterior flap and in combination with abdomino-perineal amputation and colostomy in one case. Results: At 4 years of follow-up, case one is living a relatively normal life. She had an uncomplicated pregnancy and a cesarean section delivery. Case two underwent emergency surgery for intestinal perforation and sepsis. She died 2.5 months following the surgery. Conclusion: External hemipelvectomy for soft tissue sarcoma treatment is a demanding surgical procedure with purpose in selected cases after review by multidisciplinary committees and with informed patient consent. This should be similarly individualized and extended to other pathologies when possible

Cancer cells display elevated reactive oxygen species (ROS) and altered redox status, Here based on these characteristics, we develop a multi-drug delivery platform AMB@PDAP-Fe (APPF), from magnetotactic bacterium AMB-1 and realize MRI-visualized tumor microenvironment-responsive photothermal-chemodynamic therapy. The Fe3+ in PDAP-Fe is reduced by the GSH at tumor site and is released in the form of highly active Fe2+, which catalyzes the generation of ROS through Fenton reaction and inhibits tumor growth. At the same time, the significant absorption of the mineralized magnetosomes in AMB-1 cells in the NIR region enable them to efficiently convert near-infrared light into heat energy for photothermal therapy (PTT), to which PDAP also contributes. The heat generated in the PTT process accelerates the process of Fe2+ release, thereby achieving an enhanced Fenton reaction in tumor microenvironment. In addition, the magnetosomes in AMB-1 are used as MRI contrast agent, and the curing process is visualized. This tumor microenvironment-responsive MTB-based multi-drug delivery platform displays a potency to combat tumor and demonstrates the utility and practicality of understanding the cooperative molecular mechanism when designing multi-drug combination therapies.

Following the transfer of hospital services to provincial government oversight, it is essential to understand how such changes impact service quality and efficiency. This study aims to identify the factors affecting hospital service quality post-transfer and evaluate the role of professional nurses in maintaining service standards under new governance.We conducted the study at sub-district health-promoting hospitals using a mixed-methods design based on the Global Fund-HSS framework (2012), which categorizes factors into accessibility, processes, productivity, and outcomes. We collected data from 340 nurses and 400 patients using structured questionnaires. We divided the questionnaires into seven sections, which captured a range of metrics such as the personal data of nurses, hospital service activities, and leadership qualities. We employed a Likert scale to gauge perceptions and expectations of service quality. We used paired t-tests to compare performance metrics before and after the administrative transfer, one-way ANOVA to assess variability among different service units, and binary logistic regression to identify key determinants of service quality in our statistical analysis. The analysis revealed a significant correlation between the attitudes and competencies of healthcare teams and the levels of service quality. Notably, service units transferred less than 50% exhibited minimal changes, indicating that the degree of transfer significantly impacts service outcomes. Despite these variations, the fundamental mission of promoting health remained consistent. The study emphasizes the critical role of nurses and recommends further research to identify additional factors that could improve service quality in transferred healthcare facilities. This could contribute to improved healthcare delivery across restructured health systems.

Following the transfer of hospital services to provincial government oversight, it is essential to understand how such changes impact service quality and efficiency. This study, conducted from 1 March 2023 to 31 March 2024 at sub-district health-promoting hospitals in Thailand, aims to identify the factors affecting hospital service quality post-transfer and evaluate the role of profes-sional nurses in maintaining service standards under new governance. Utilizing a mixed-methods design based on the Global Fund-HSS framework (2012), which categorizes factors into accessibility, processes, productivity, and outcomes, we collected data from 340 nurses and 400 patients through structured questionnaires. These questionnaires were divided into seven sec-tions, capturing metrics such as the personal data of nurses, hospital service activities, and lead-ership qualities. We employed a Likert scale to gauge perceptions and expectations of service quality and conducted paired t-tests to compare performance metrics before and after the admin-istrative transfer. One-way ANOVA was used to assess variability among different service units, and binary logistic regression helped identify key determinants of service quality. The analysis revealed a significant correlation between the attitudes and competencies of healthcare teams and the levels of service quality. Notably, service units transferred less than 50% exhibited mini-mal changes, indicating that the degree of transfer significantly impacts service outcomes. Despite these variations, the fundamental mission of promoting health remained consistent. The study emphasizes the critical role of nurses and recommends further research to identify additional factors that could improve service quality in transferred healthcare facilities, potentially contributing to enhanced healthcare delivery across restructured health systems.

Omega-3 polyunsaturated fatty acids (ɷ-3 PUFAs) offer diverse health benefits, such as supporting cardiovascular health, improving cognitive function, promoting joint and musculoskeletal health, and contributing to healthy aging. Despite their advantages, challenges like oxidation susceptibility, low bioavailability, and potential adverse effects at high doses persist. Nanoparticle encapsulation emerges as a promising avenue to address these limitations while preserving stability, enhanced bioavailability, and controlled release. This comprehensive review explores the therapeutic roles of omega-3 fatty acids, critically appraising their shortcomings and delving into modern encapsulation strategies. Furthermore, it explores the potential advantages of Metal-organic framework nanoparticles (MOF NPs) compared to other commonly utilized nanoparticles in improving the therapeutic effectiveness of omega-3 fatty acids within drug delivery systems (DDS). Additionally, it outlines future research directions to fully exploit the therapeutic benefits of these encapsulated omega-3 formulations for cardiovascular disease treatment.

Complex-structured polymeric microparticles hold significant promise as advance in next-generation medicine mostly due to demand from developing targeted drug delivery. However, the conventional methods for producing these microparticles of defined size, shape and sophisticated composition often face challenges in scalability, reliance on specialized components such as micro-patterned templates, or have limited control over particle size distribution and cargo release kinetics. In this study, we introduce a novel and reliably scalable approach for manufacturing microparticles of defined structures and sizes with variable parameters. The concept behind this method involves the deposition of a specific number of polymer layers on a substrate with low surface energy. Each layer can serve as either the carrier for cargo or a programmable shell-former with predefined permeability. Subsequently, this layered structure is precisely cut into desired-sized blanks using a laser. The manufacturing process is completed by applying of heat to the substrate what results on sealing the edges of the blanks. The combination of the high surface tension of the molten polymer and the low surface energy of the substrate enables the formation of discrete particles, each possessing semi-spherical or other designed geometries determined by their internal composition. Such anisotropic microparticles are envisaged versatile applications.

Introduction: Desmoid tumor (DT) is a rare benign neoplasm rising from muscle aponeurosis, having been associated mostly with trauma or pregnancy. DT has an infiltrative and locally aggressive growth pattern and usually does not metastasize. However, it has a high recurrence and complication rate. When they occur in pregnancy, are all pregnancies and deliveries taken as individual case for optimal management by the physicians and midwifes, who need to be cautious in finding the optimal delivery mode for patients, which depends on tumor size, location, behavior and past history. Study Objectives: We present a case report of a large desmoid tumor of the anterior abdominal wall in a 29-year-old woman in pregnancy, presenting a delivery problem, which resolved in surgical management. Moreover, we are bringing a systematic review of the literature to provide an overview on pathomechanism, symptoms, diagnostics and treatment management of the pregnant women affected by DT. Results: The authors report a case of pregnant women who underwent systemic oncological treatment for abdominal wall desmoid tumor and have been pregnant afterwards. The observational conservative management was chosen with an elective cesarean section at the 38+4 pregnancy week with uncomplicated postpartum follow-up. Conclusion: Pregnancy-associated desmoid tumors are very rare and optimal management of this tumor is not well established, despite some guidelines for non-pregnant patients. The authors reviewed the literature focusing on the actual modern management of desmoid tumors at all, including patients during the pregnancy, as well.

Prostate-specific membrane antigen (PSMA) has been identified as a target for the development of theranostic agents. In our current work, we describe the design and synthesis of novel N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-L-lysine (DCL) urea-based PSMA inhibitors with a chlorine-substituted aromatic fragment at the lysine ε-nitrogen atom, a dipeptide as peptide fragment of the linker, including two phenylalanine residues in the L-configuration, and 3- or 4-(tributylstannyl)benzoic acid as prosthetic group in their structures for radiolabeling. The standard compounds ([127I]PSMA-m-IB and [127I]PSMA-p-IB) for comparative and characterization studies were firstly synthesized using two alternative synthetic approaches. An important advantage of the alternative synthetic approach in which the prosthetic group (NHS-activated esters of compounds) is first conjugated with the polypeptide sequence, followed by replacement of the Sn(Bu)3 group with radioiodine, is that the radionuclide is introduced in the final step of synthesis, thereby minimizing operating time with iodine-123 during the radiolabeling process. The obtained DCL urea-based PSMA inhibitors were radiolabeled with iodine-123. The radiolabeling optimization results showed that the radiochemical yield of [123I]PSMA-p-IB was higher than those of [123I]PSMA-m-IB, which were 74.9± 1.0% and 49.4 ± 1.2%, respectively. The radiochemical purity of [123I]PSMA-p-IB after purification was greater than 99.50%. The initial preclinical evaluation of [123I]PSMA-p-IB demonstrated a considerable affinity and specific binding to PC-3 PIP (PSMA-expressing cells) in vitro. The in vivo biodistribution of this new radioligand [123I]PSMA-p-IB showed less accumulation than [177Lu]Lu-PSMA-617 in several normal organs (liver, kidney and bone). These results warrants further preclinical development including toxicology evaluation and experiments in tumor-bearing mice.

In the vaginal ecosystem there is a symbiotic relationship between the microbiota and the host, particularly Candida spp., which are considered commensals of the vaginal mucosa. During pregnancy there is an increase in hormonal secretion that alters the vaginal microbiota and favors the development of Candida infection. Several studies have shown the increased prevalence of Candida during pregnancy, as well as its association with perinatal complications and current clinical practice guidelines recommend fluconazole as the treatment of choice during pregnancy in case of infection by Candida albicans and non-albicans Candida. However, in the Mexican population, this association has not been studied. So in this study, an intentional search for colonization by Candida spp. in pregnant women who attended the obstetric triage of the Hospital Regional de Alta Especialidad de Ixtapaluca during the period from May to October 2019, and they were followed up until the end of the pregnancy. Data on age, number of pregnancies, gestational age, body mass index, and perinatal outcomes were analyzed. Of 83 patients included in the study, yeasts corre-sponding to C. albicans (12) and C. glabrata (4) were isolated in 16. In the group of patients with Candida, the maternal age range was from 15 to 36 years old, of which 7 were adolescents and 2 with advanced maternal age, with an average of 2 gestations, the range of body mass index was from 19.3 to 42.4, of which 4 were overweight and 7 obese. Perinatal complications were observed in three patients, one presented chorioamnionitis and in two the neonates were small for gestational age. No association was found between colonization by Candida spp. and the number of preg-nancies, gestational age, body mass index or perinatal results. However, it was found that age (adolescence) may be a risk factor for the development of vulvovaginitis during pregnancy.

Elevated levels of oxidative stress in the corneal epithelium contribute to the progression of dry eye disease pathology. Previous studies have shown that antioxidant therapeutic intervention is a promising avenue to reduce disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of Xanthohumol in preclinical models for dry eye disease. Xanthohumol is a naturally occurring prenylated chalconoid that promotes the transcription of phase II antioxidant enzymes. Xanthohumol exerted a dose-response in preventing tert-butylhydroxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells and resulted in a significant increase in expression of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of the endogenous antioxidant system. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced corneal fluorescein staining in the mouse desiccating stress/ scopolamine model for dry eye disease in vivo by reducing oxidative stress-associated DNA damage in corneal epithelial cells. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been considered a promising therapeutic approach to cardiovascular disease. This study intends to compare the effect of BMSCs through a standard active cardiac support device (ASD) and intravenous injection on global myocardial injury induced by isoproterenol. BMSCs were cultured in vitro, and the transplanted cells were labeled with a fluorescent dye CM-Dil. Isoproterenol (ISO) was injected into the rats; two weeks later, the labeled cells were transplanted into ISO-induced heart-injury rats through the tail vein or ASD device for five days. The rats were sacrificed on the first day, the third day, and the fifth day after transplantation to observe the distribution of cells in the myocardium by fluorescence microscopy. The hemodynamic indexes of the left ventricle were measured before sacrificing. H&E staining and Masson’s trichrome staining were used to evaluate the cardiac histopathology. In the ASD groups, after three days of transplantation, there were many BMSCs on the epicardial surface, and after five days of transplantation, BMSCs were widely distributed in the ventricular muscle. But in the intravenous injection group, there were no labeled-BMSCs distributed. In the ASD+BMSCs-three days treated group and ASD+BMSCs -five days-treated group, left ventricular systolic pressure (LVSP), the maximum rate of left ventricular pressure rise (+dP/dt), the maximum rate of left ventricular pressure decline (-dP/dt) increased compared with model group and intravenous injection group (P<0.05). By giving BMSCs through ASD device, cells can rapidly and widely distribute in the myocardium and significantly improve heart function.

The construction industry is one of the most fatal industries, so it is important to pay more attention to safety solutions. Even though work-related accidents are known as major waste in construction projects, little attention has been paid so far to incorporating safety into the lean construction framework. In this research, lean construction theory is reviewed through the lens of safety. That being so, the identified challenges in previous research on improving safety in construction projects are categorized and those related to the concept of lean project delivery are introduced. Then, the principles of the lean construction framework are explained and the relevant changes for incorporating safety into the framework are introduced and discussed. It is expected that this hybrid model would further enrich the lean construction framework. The careful attention of project executives to this model may improve the safety situation in construction projects.

Background: As noninvasive prenatal screening usage grows in the general obstetrics setting, proper patient education on the screen’s benefits and limitations is needed. Objective: Describe the use of a technology platform designed for large-scale dissemination of noninvasive prenatal screening information and results. Study Design: The technology platform functioned as follows: Patients were emailed a link to an noninvasive prenatal screening general-education video upon laboratory receipt of a test requisition. Providers were then notified upon availability of patients’ results. If noninvasive prenatal screening results were negative, the patient was sent an automated email with instructions to access results through a secure portal where she could watch tailored informational videos, request “on-demand” or scheduled genetic counseling, or decline any further services. If genetic counseling was elected, a summary of the session was sent to the ordering provider and patient upon completion. If noninvasive prenatal screening results were positive, either the ordering provider or a board-certified genetic counselor contacted the patient directly to communicate test results and provide counseling. The number and type of results issued through the platform, the number and type of genetic counseling consultations completed, and factors associated with requesting laboratory-delivered genetic counseling were tracked and analyzed for a 39-month period. Results: Over the study period, 67,122 noninvasive prenatal screening results were issued through the platform, and 4,673 patients elected genetic counseling consultations; 95.2% (n=4,450) of consultations were for patients receiving negative results. Over 70% (n= 3,370) of consultations were on-demand rather than scheduled. Median consultation time was 14 minutes for positive results and six minutes for negative results. A positive screen, advanced maternal age, family history, previous history of a pregnancy with a chromosomal abnormality, and other high-risk pregnancy were associated with the greatest odds of electing laboratory-delivered genetic counseling. Conclusions: By combining web education, automated notifications, and genetic counseling, we implemented a service that effectively facilitates results disclosure for ordering providers. These data demonstrate the capability to deliver noninvasive prenatal screening results, education, and counseling—congruent with management guidelines—to a large population, which is imperative to quality care as uptake increases.

This work is concerned with studying the change of some Optical and Electrical Properties of Ba_xFe_(1-x)TiO₄ thin films due to the change of the nano crystal size. Simple theoretical explanation based on the string theory was developed. The empirical results obtained indicated that the absorption coefficient, electrical conductivity, and the magnetic permeability increase upon decreasing the nano crystal size. However, the transmission coefficient, and the refractive index increase upon increasing the nano crystal size. All these changes are explained using a simple string model with the aid of Newton's laws. The capability of the string theory to explain this nano quantum behavior comes from the fact that the string theory recognize both the particle and the wave nature of the nano system. This is similar of course to the quantum approach which is based mainly on the dual wave particle nature of atomic systems and entities.

Control of autonomous robot motion in radial mass density field is presented. In that sense the robot motion is described as the function of the radial mass density parameters. The radial mass density field is between the maximal radial mass density and the minimal radial mass density. Between these two limited values one can use n points (n = 1, 2, . . . nmax) and calculate the related radial mass density for each point. The radial mass density is maximal at the minimal gravitational radius and minimal at the maximal gravitational radius. This conclusion is valid for Planck scale, but also for the scales that are less or higher of that one. Using the ratio of the Planck mass and Planck radius it is generated energy conservation constant with value κ = 0.99993392118. Further, in this theory it is possible to connect Planck’s and gravitational parameters as functions of the maximal (or minimal) radial mass density. In that sense the autonomous robot motion in radial mass density field is important for the control of the robot motion at micro and nano scales.

Biosensors are measurement devices that can sense several biomolecules, and are widely used for the detection of relevant clinical pathogens such as bacteria and viruses, showing outstanding results. Because of the latent existing risk of facing another pandemic like the one we are living due to COVID-19, researchers are constantly looking forward to developing new technologies for diagnosis and treatment of infections caused by different bacteria and viruses. Regarding that, nanotechnology has improved biosensors design and performance through the development of materials and nanoparticles that enhance their affinity, selectivity, and efficacy in detecting these pathogens, such as employing nanoparticles, graphene quantum dots, and electrospun nanofibers. Therefore, this work aims to present a comprehensive review that exposes how biosensors work in terms of bacterial and viral detection, and the nanotechnological features that are contributing to achieving a faster yet still efficient COVID-19 diagnosis at the point-of-care.

Direct laser writing three-dimensional nano-lithography is an established technique for manufacturing functional 3D micro- and nano-objects via non-linear absorption induced polymerization process. In this Chapter an underlying physical mechanisms taking place during nano-confined polymerization reaction, induced by tightly focused ultra-short laser pulses, are reviewed and discussed. The special attention is paid on the effects that directly impact structuring resolution and minimum achievable feature size. Analysis of possible photo-initiation mechanisms as contributing multi-photon absorption and avalanche ionization in pre-polymers under diverse exposure conditions (wavelength, pulse duration) is presented. Feasible structuring of pure (non-photosensitized) and functional nanoparticles doped polymer precursors is justified and benefits of such materials/structures for microoptics, photonics and cell scaffolds are highlighted. The influence of temperature effects (induced by writing process itself or determined by ambient conditions) on polymerization process, observed in different pre-polymers under diverse exposure regimes is outlined. The further adjustment of the structuring resolution is possible via precise control of light polarization and diffusion assisted radical quenching. The work is concluded with a brief outlook on future challenges and perspectives related to refinement of 3D ultra-fast laser lithography fabrication process in the means of application of diverse post-processing methods and research into novel photo-curable materials including inorganic ones.

Given the rise in the number of cases and their recurrences, Urinary Tract Infections (UTI) are one of the major burdens on public healthcare worldwide. Rapid, inexpensive and selective detection of Uropathogenic E. coli (UPEC), a major contributor to UTIs, is the need of the hour for effective treatment, given the rise of antibiotic-resistant bacteria due to improper diagnosis. Here we present a rapid, real-time, selective and label-free detection of UPEC using an integrated sensing platform based on Crossed Surface Relief Gratings (CSRGs) as nanoplasmonic sensors. Detection is achieved due to the unique Surface Plasmon Resonance (SPR)-based light energy exchange attributed to the CSRGs, allowing real-time sensing in a very narrow bandwidth of the incident light to pass where the SPR energy conversion occurs. The sensing ability of the platform is experimentally demonstrated by the detection of bulk Refractive Index (RI) changes, with a bulk sensitivity of 382.2 nm/RIU and a resolution in the order of 10-6 RIU. We demonstrate selective capture and detection of clinical concentration of UPEC, as opposed to other gram-negative bacteria, in real-time, a first for CSRGs. This work is particularly important for effective treatment of UTIs, allowing point-of-care diagnosis for economically disadvantaged regions around the world.

A new generation of nano-technologies is expanding solid propulsion capabilities and increasing their relevance for versatile and manoeuvrable micro-satellites with safe high-performance propulsion. We propose the innovative concept, connected with application of new synergistic effect of the energetic materials performance enhancement and reaction zones programming for the next generation small satellite multimode solid propulsion system. The main idea of suggested concept is manipulating by the self-organized wave patterns excitation phenomenon, by the properties of the energetic materials reaction zones and by localization of the energy release areas. This synergistic effect can be provided through application of the functionalized carbon-based nanostructured metamaterials as a nano-additives along with simultaneous manipulating by their properties through the electrostatic field. Mentioned effect will be controlled through predictive programming both by the spatial structure and physics-chemical properties of the functionalized carbon-based nano-additives and through the electromagnetic control of the self-organized wave pattern excitation and micro- and nano- scale oscillatory networks in the energetic material reaction zones. Suggested new concept makes it possible to increase the energetic material regression rate and increase the thrust of the solid propulsion system with minimal additional energy consumption.

Dispatching goods is becoming more difficult to manage in the field of logistics due to the high demand for order shipments. This is relative to the increasing popularity of the use of e-commerce platforms among consumers, where delivery of products is required as compared to buying in physical stores. Dispatch management is one of the critical components in a supply chain since it covers the coordination tasks among stakeholders from warehouse up to the consumer’s doorstep. In this study, the authors intend to propose a framework leveraging geographic information to sustain the logistics operations, specifically in terms of managing last-mile delivery and return trip orders. This includes scheduling, communications, and inventory of goods shipment. A mobile application built on this framework was integrated with a waypoint order optimization algorithm considering the entire route traversing all the required pick-up and delivery points. It was pilot tested with an actual dispatch operation of a logistics company yielding a decrease of 87% in total shipment time, 79% in operations cost, and 3% in carbon footprint per vehicle. With the adoption of this framework, the study aims to contribute to the overall efficiency and sustainability of logistics operations in a wider geographic range.

Supplier Relationship Management (SRM) plays a pivotal role in enhancing delivery performance within the e-commerce sector, yet understanding its nuanced impacts remains crucial for optimizing operational efficiencies and customer satisfaction. This qualitative research explores the intricate dynamics of SRM in e-commerce, focusing on strategic alignment, technological integration, trust, collaboration, and risk management as key determinants of delivery reliability. Through in-depth interviews and thematic analysis, the study reveals that strategic alignment of supplier capabilities with firm objectives is fundamental for maintaining a responsive and synchronized supply chain. Technological integration, including AI-driven analytics and blockchain applications, emerges as critical for real-time monitoring and adaptive decision-making, thereby improving delivery accuracy and efficiency. Trust and collaboration are identified as essential pillars for building resilient supplier relationships, fostering transparent communication and joint problem-solving. Effective risk management practices, such as supplier diversification and contingency planning, mitigate disruptions and ensure consistent delivery performance. Despite these benefits, challenges such as technological adoption barriers, cultural differences, communication complexities, resource constraints, and supplier reliability issues persist, necessitating strategic interventions. Recommendations include investing in advanced SRM technologies, promoting cultural understanding, enhancing communication protocols, allocating adequate resources, and fostering collaborative initiatives with suppliers. These strategies aim to overcome challenges and optimize SRM practices, ultimately enhancing delivery performance and competitiveness in the e-commerce landscape.

Transdermal drug delivery systems (TDDS) are designed to administer a consistent and effective dose of medication through the patient's skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. This medication provides a continuous and prolonged administration of a substance at a consistent rate. TDDS, or transdermal drug delivery system, has gained significant attention as a non-invasive method of administering drugs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first-pass metabolism and the corrosive acidic environment of the stomach that happens when medications are taken orally. Multiple methodologies have been devised to augment the transdermal permeability of diverse pharmaceutical substances. Recent advancements in transdermal drug delivery systems have facilitated the precise delivery of medications to the intended site of action by improving the penetration of drugs through the outermost layer of the skin, known as the stratum corneum, resulting in enhanced drug availability throughout the body. This review seeks to provide a concise overview of the several methods employed in the production of TDDS, as well as their evaluation, therapeutic uses, clinical considerations, and current advancements. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient transdermal drug delivery systems.

Recently, nanotechnologies have become increasingly prominent in the field of bone tissue engineering (BTE), offering substantial potential to advance the field forward. These advancements manifest in two primary ways: the localized application of nanoengineered materials to enhance bone regeneration and their use as nano-vehicles for delivering bioactive compounds. Despite significant progress in the development of bone substitutes over the past few decades, it is worth noting that the quest to identify the optimal biomaterial for bone regeneration remains a subject of intense debate. Ever since its initial discovery, poly(lactic-co-glycolic acid) (PLGA) has found widespread use in BTE due to its favorable biocompatibility and customizable biodegradability. This review provides an overview of contemporary advancements in the development of bone regeneration materials using PLGA polymer. The review covers some of PLGA properties with a special focus on modifications of these properties towards bone regeneration. Furthermore, we delve into the techniques for synthesizing PLGA nanoparticles (NPs), the diverse forms in which these NPs can be fabricated, and the bioactive molecules that exhibit therapeutic potential for promoting bone regeneration. Additionally, we addressed some of the current concerns regarding the safety of PLGA NPs, and PLGA-based products available in the market. Finally, we briefly discussed some of the current challenges and proposed some strategies to functionally enhance the fabrication of PLGA NPs towards BTE. We envisage that the utilization of PLGA NP holds significant potential as a potent tool in advancing therapies for intractable bone diseases.

Treatment of various diseases, in particular cancer, usually needs targeting biologically active molecules at a selected subcellular compartment. We modified our previously developed modular nanotransporters (MNTs) for targeting mitochondria. The new MNTs are capable of binding to the protein predominantly localized on the outer mitochondrial membrane, Keap1. These MNTs possessing antiKeap1 monobody co-localize with mitochondria upon addition to the cells. They efficiently interact with Keap1 both in solution and within living cells. A conjugate of the MNT with a photosensitizer, chlorin e6, demonstrates significantly higher photocytotoxicity than chlorine e6 alone. We assume that MNTs of this kind can improve efficiency of therapeutic photosensitizers and radionuclides emitting short-range particles.

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

Background: Post-delivery period could be characterized by psychological distress (e.g., anxiety, sadness, and irritability), leading to post-partum depression (PPD). Objective: The present clinical study assess the effect of probiotic supplementation containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) on mother’s mood and breastfeeding quality during the first trimester after delivery. Methods: A Randomized Double Blind Controlled (RDBPC) trial has been carried out in 200 healthy new mothers divided into an active group taking a supplement containing Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 (4x10⁹ CFU/day) plus multivitamins, and a control group (multivitamin complex only) for 90 days. Symptoms related to maternal depression and breastfeeding quality were evaluated at days 45 and 90 by Edinburgh Postnatal Depression Scale (EPDS) and Breastfeeding Self-Efficacy Scale Short-Form (BSES-SF). Results: At days 45 and 90, probiotic treatment significantly ameliorated the mothers’ mood compared to the control treatment (p<0.001). Likewise, breastfeeding quality and baby’s cries significantly improved in the probiotic group (p<0.001). Conclusions: Microbiota alterations could influence post-delivery woman’s mental state. According to our results, L. reuteri PBS072 and B. breve BB077 are potential candidates able to improve stress resilience in the post-partum period.

Synthetic antivirals and corticosteroids have been used to treat both influenza and the SARS-CoV-2 disease named COVID-19. However, these medications are not always effective, produce several adverse effects, and are associated with high costs. Medicinal plants and their constituents act in several different targets and signaling pathways involved in the pathophysiology of Influenza and COVID-19. This study aimed to perform a review to evaluate the effects of medicinal plants on Influenza and COVID-19 and to investigate the potential delivery systems for new antiviral therapies. EMBASE, PubMed, GOOGLE SCHOLAR, and COCHRANE databases were searched. The studies included in this review showed that medicinal plants, in different formulations, can help decrease viral spread and time of full recovery. Plants reduced the incidence of acute respiratory syndromes and the symptom scores of the illnesses. Moreover, plants are related to few adverse effects and have low costs. In addition to their significance as natural antiviral agents, medicinal plants and their bioactive compounds may exhibit low bioavailability. This highlights the need for alternative delivery systems, such as metal nanoparticles, that can effectively transport these compounds to infected tissues.

Because of their high biocompatibility, stability, ability to negotiate biological barrier passage, and functionalization properties, biological nanoparticles have been actively investigated for many medical applications. Biological nanoparticles, including natural extracellular vesicles (EVs) and synthetic extracellular vesicle-mimetic nanovesicles (EMNVs) represent novel drug delivery vehicles that can accommodate different payloads. In this study, we investigated EVs and EMNVs for their physical, biological and delivery properties and we showed that EMNVs have similar delivery properties compared to EVs. In addition, these nanotherapeutics were analyzed for their cytostatic properties in combination with the FDA-approved drug hydroxychloroquine (HCQ), which increased their cytostatic thanks to its lysosome-destabilizing properties. Altogether, these data demonstrated that, at least in vitro, the use of synthetic biomimetic particles is comparable to the natural counterparts, while their synthesis is significantly faster and more cost effective. In addition, we highlighted the benefits of combining biological nanoparticles with a lysosome destabilizing agent that increased the delivery properties of the particles.

Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life and poor penetration into HIV reservoir sites, which contribute to the sub-optimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review focus on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARVs to overcome biological barriers upon administration. Furthermore, a correlation of these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference delivery for the treatment of HIV infections were also discussed.

Non-viral gene carriers because of their limited side effects, biocompatibility, simplicity and taking the advantages of electrostatic interactions have shown noticeable potential in gene delivery. The low transfection rate of non-viral vectors under physiological conditions is a significant issue. Here, the aim of this study was to investigate the efficacy of hydrophilic and hydrophobic groups on gene carriers such as two synthesized amphiphilic polymer of dextran-stearic acid-spermine (DSASP) with verified lipid and amine conjugations that associated with Fe3O4 superparamagnetic nanoparticles to promote the target delivery and decrease the transfection time using static magnetic field. Our findings illustrate that magnetic nanoparticles are spherical with positive surface charges and superparamagnetic behaviors. The DSASP–pDNA/MNPs offered a strong pDNA condensation, protection against DNase degradation, significant cell viability in HEK 293T cells and. Although conjugations of spermine play a critical role in transfection efficiency, amphiphilic polymer with more derivatives of stearic acid showed better transfection yields. Therefore, DSASP amphiphilic magnetic carriers offer new insights for gene delivery due to the amine contents and ameliorate the uptake of complexes via cell membrane based on its hydrophilic surface.

With the COVID-19 pandemic now ongoing for close to a year, people all over the world are still waiting for a vaccine to become available. The initial focus of accelerated global research and development efforts to bring a vaccine to market as soon as possible was on novel platform technologies that promised speed but had limited history in the clinic. In contrast, recombinant protein vaccines, with numerous examples in the clinic for many years, missed out on the early wave of investments from government and industry. Emerging data are now surfacing suggesting that recombinant protein vaccines indeed might offer an advantage or complement to the nucleic acid or viral vector vaccines that will likely reach the clinic faster. Here, we summarize the current public information on the nature and on the development status of recombinant subunit antigens and adjuvants targeting SARS-CoV-2 infections.

Intranasal (i.n.) administration became an alternative strategy to bypass the blood-brain barrier and improve drug bioavailability in the brain. The main goal of this work was to preliminarily study the biodistribution of mixed amphiphilic mucoadhesive nanoparticles made of chitosan-g-poly(methyl methacrylate) and poly(vinyl alcohol)-g-poly(methyl methacrylate) and ionotropically crosslinked with sodium tripolyphosphate in the brain after intravenous (i.v.) and i.n. administration to Hsd:ICR mice. After i.v. administration, the highest nanoparticle accumulation was detected in the liver, among other peripheral organs. After i.n. administration of a 10-times smaller nanoparticle dose, the accumulation of the nanoparticles in off-target organs was much lower than after i.v. injection. In particular, the accumulation of the nanoparticles in the liver was 20 times lower than by i.v. When brains were analyzed separately, intravenously administered nanoparticles accumulated mainly in the “top” brain, reaching a maximum after 1h. Conversely, in i.n. administration, nanoparticles were detected in the “bottom” brain and the head (maximum reached after 2 h) owing to their retention in the nasal mucosa and could serve as a reservoir from which the drug is released and transported to the brain over time. Overall results indicate that i.n. nanoparticles reach similar brain bioavailability, though with a 10-fold smaller dose, and accumulate in off-target organs to a more limited extent and only after redistribution through the systemic circulation. At the same time, both administration routes seem to lead to differential accumulation in brain regions and thus, they could be beneficial in the treatment of different medical conditions.

The development of targeted therapeutics for cancer continues to receive intense research attention as laboratories and pharmaceutical companies seek to develop drugs and technologies that improve treatment efficacy and mitigate harmful side effects. In the aftermath of World War I, it was discovered that mustard gas destroys rapidly dividing cells and could be used to treat cancer. Since then, chemotherapy has remained a predominant treatment for cancer; however, the destruction of dividing cells throughout the body yields devastating side effects including off-target damage of the digestive tract, bone marrow, skin, and reproductive tract. Furthermore, the high mutation rate of cancerous cells often renders chemotherapy ineffective long-term. Therapies with improved specificity, localization, and efficacy are redefining cancer treatment. Herein, we define and summarize the principal advancements in targeted cancer treatment and briefly comment on the march towards personalized medicine in the treatment of human cancer.

Since its introduction, the Triangulation number has been the most successful and ubiquitous scheme for classifying spherical viruses. However, despite its many successes, it fails to describe the relative angular orientations of proteins, as well as their radial mass distribution within the capsid. It also fails to provide any insight into critical sites of stability, modifications or possible mutations. We show how classifying spherical viruses using icosahedral point arrays, introduced by Keef and Twarock, unveils new geometric rules and constraints for understanding virus stability and key locations for exterior and interior modifications. We present a modified fitness measure which classifies viruses in an unambiguous and rigorous manner, irrespective of local surface chemistry, steric hinderance, solvent accessibility or triangulation number. We then utilize these point arrays to explain the immutable surface loops of bacteriophage MS2, the relative reactivity of surface lysines in CPMV and the non-quasiequivalent flexibility of the HBV dimers. We explain how using sister and double point arrays can function as predictive tools for site directed modifications in other systems. This success builds on our previous work showing that viruses place their protruding features along the great circles of the asymmetric unit, demonstrating that viruses indeed adhere to these geometric constraints.

The release profiles of methotrexate, an anticancer drug, from the monoolein liquid crystalline cubic phases were studied. The cubic phases were used either in the form of a lipidic film deposited onto a glassy carbon electrode surface or in the dispersed form of magnetocubosomes, which are considered a prospective hybrid drug delivery system. Commonly, cubosomes or liposomes are employed, but not in the case of toxic methotrexate, known to block receptors responsible for folate transport into the cells. The release profiles of the drug from the lipidic films were monitored electrochemically and described using the Higuchi model. They were also modified via changes in temperature; the release was faster, although deviating from the model when the temperature was increased. Magnetocubosomes - cubic phase nanoparticles containing hydrophobic magnetic nanoparticles placed in an alternating magnetic field of low frequency and amplitude, stimulated drug release from the suspension, which was monitored spectroscopically. These new biocompatible hybrid materials are very promising, allowing to control the release of the drug at the appropriate sites, but do require further investigations into their in vitro cytotoxicity and in vivo biodistribution.

In the fifth generation communication system, millimeter wave (mmWave) networks will coexist with traditional micro wave (μWave) networks, which allows for higher data transmission rate and better user experience. In this paper, we give a comprehensive framework of mathematical models and analytical methods for multi-tier mmWave and μWave hybrid caching networks based on stochastic geometry. We propose an association strategy by assuming average biased-received power association and Rayleigh fading. Accordingly, by using a D-ball approximating blockage model of mmWave networks, expressions of the cell association probability and the coverage probability of the hybrid networks are derived. Also, we use the average successful delivery probability as the performance metric to analyze the existing caching placement strategies. Simulation results validate the accuracy of our analytical conclusions.

Two pilot scale desalination system employing carbon modified nano-sized, zero valent metals (n-ZVM) were maufactured and tested to determine (1) the degree to which high salt water (20 to 130 mS) could be desalinated and (2) if this degree of desalination could be maintained throughout an extended treatment period. Two pilot systems were tested (referred to as Generation 1 and Generation 2) consisting of parallel lines of 4 individual reactors in series, a settling tank and an activated carbon cell at the end of each reactor line. The system capacity was 300 gal in Generation 1 and 600 gal in Generation 2 total with a total hydraulic residence time of 6 hours per reactor line (one hour per cell/tank). A slurry of n-ZVM was introduced in the first reactor on each line to yield approximately 5 to 45 grams of nano-metal per 100 L of influent salt water. The n-ZVM slurry was made from mixing tea extract with metal salts (eg ferrous sulfate, ferric chloride) to produce the carbon modified metal slurry. Initial runs focused on dosing required to achieve maximum salt removal at each of three influent salt contents, 28 mS, 44 mS and 123 mS. Once dosing was set, continuous runs (14 days, 23 days and 9 days) were carried out to (1) examine the ability of the pilot to maintain the removal efficiency over an extended period, (2) to determine the weaknesses inherent in the pilot systems, and (3) to begin to develop CAPEX and OPEX estimates for the pilot and pre-design full scale mobile desalination unit (MDU) system. Results demonstrated that maximum removal occurred with 10 g/100L of salt for the 30 mS salt solution,16 g/100 L of salt for the 40 mS influent water and 40 g/100 L for the 130 mS influent. Salt removal (expressed as Na and Cl removed) approached 78% for the 30 mS influent and 41 mS influent respectively while removal for the highest salt influent (130 mS) approached 81 %. Addition of greater amounts of carbon modified slurry than those described resulted in a pH less than 6 which inhibits continued salt removal and would require addition of calcium or magnesium oxides/hydroxides or bicarbonate solutions at the influent side to achieve greater salt removal and of course greater cost per gallon. Continuous operation over the extended time-period showed no significant decrease in salt removal with typical day to day variation of no more than 10% suggesting that this approach to desalination could rapidly provide usable water from saline aquifers, seawater or even produced water. Treatment of saline waters at 30 mS or less yields effluent water in the range necessary for irrigation use of many crops while treatment of seawater or produced water levels of salt (40 mS or higher) yields effluent in the range of 8 to 10 mS a range ideal for RO influent that would prevent the production of large volumes of brine. Pilot testing continues with seawater extracted from Puget Sound, Seattle WA and higher levels of salt to better represent produced water.

Accumulation of proteins in filter membranes limits the efficiently of filtering technologies for cleaning wastewater. Efforts are ongoing to coat commercial filters with different materials (such as titanium-dioxide, TiO2) in order to reduce the fouling of the membrane. Beyond monitoring the desired effect of retention of biomolecules, it is demanding to understand what are the biophysical changes in water-soluble proteins caused by interacting with the new coated filter membranes, an aspect that has received little attention so far. Using spin label electron paramagnetic resonance (EPR), aided with native fluorescent spectroscopy and dynamic light scattering (DLS), here we report the changes in the structure and dynamics of bovine serum albumin (BSA) exposed to TiO2 (P25) nanoparticles or passing through commercial polyvinylidene fluoride (PVDF) membranes coated with the same nanoparticles. We have found that the filtering process and prolongued exposure to TiO2 nanoparticles had significant effects on different regions of BSA, and denaturation of the protein was not observed, neither with TiO2 nanoparticles nor by pressing through TiO2-coated filter membranes.

In this paper, various Ni-P composite coatings containing toner, MoS2, and nano-SiO2 particles were deposited on steel substrates by the electroless method. Then, the electrochemical properties of these coatings after a heat treatment process were compared. The microstructural evaluations were also done by using the optical and electron microscopy methods. Both Tafel polarization and electrochemical impedance spectroscopy techniques were utilized to survey the electrochemical behavior of such coatings. The surface morphology of all coatings contained cauliflower-like nodules. The X-ray diffraction patterns showed the crystalline phases of Ni and Ni3P for all coatings after the heat-treatment step. Obtained results showed that all composite coatings exhibited lower corrosion rates with respect to Ni-P coatings. Such a reduction was about 21.6-92.2%. This behavior was attributed to the presence of reinforcement as barriers for corrosive ion diffusion through the coating plus the changes in detected phases and thickness. Electrochemical impedance spectroscopy test results also demonstrated that the increase in the polarization resistance for composites coatings was about 18.4-85.3% after 1 h immersion in a 0.6M NaCl solution; however, when the immersion time increased to 24 h, such increased resistance changed to 18.1 to 73.1%. Totally, despite the lower deposition rate, the presence of MoS2 and nano-SiO2 particles were more effective than toner particles to raise the corrosion rate of the Ni-P coating.

Hand gestures may play an important role in medical applications for health care of elderly people, where providing a natural interaction for different requests can be executed by making specific gestures. In this study we explored three different scenarios using a Microsoft Kinect V2 depth sensor then evaluated the effectiveness of the outcomes. The first scenario utilized the default system embedded in the Kinect V2 sensor, which depth metadata gives 11 parameters related to the tracked body with five gestures for each hand. The second scenario used joint tracking provided by Kinect depth metadata and depth threshold together to enhance hand segmentation and efficiently recognize the number of fingers extended. The third scenario used a simple convolutional neural network with joint tracking by depth metadata to recognize five categories of gestures. In this study, deaf-mute elderly people execute five different hand gestures to indicate a specific request, such as needing water, meal, toilet, help and medicine. Then, the requests were sent to the care provider’s smartphone because elderly people could not execute any activity independently. The system transferred these requests as a message through the global system for mobile communication (GSM) using a microcontroller.

Background/Objectives: This review examines the evolution of lyotropic liquid crystals (LLCs) in ocular drug delivery, focusing on their ability to address the challenges associated with traditional ophthalmic formulations. The study aims to underscore the enhanced bioavailability, prolonged retention, and controlled release properties of LLCs that significantly improve therapeutic outcomes; Methods: The review synthesizes data from various studies on both bulk-forming LLCs and liquid crystal nanoparticles (LCNPs). It also considers advanced analytical techniques, including the use of machine learning and AI-driven predictive modeling, to forecast the phase behavior and molecular structuring of LLC systems. Emerging technologies in biosensing and real-time diagnostics are discussed to illustrate the broader applicability of LLCs in ocular health; Results: LLCs are identified as pivotal in promoting targeted drug delivery across different regions of the eye, with specific emphasis on the tailored optimization of LCNPs. The review highlights principal categories of LLCs used in ocular applications, each facilitating unique interactions with physiological systems to enhance drug efficacy and safety. Additionally, novel applications in biosensing demonstrate LLCs' capacity to improve diagnostic processes; Conclusions: Lyotropic liquid crystals offer transformative potential in ocular drug delivery by overcoming significant limitations of conventional delivery methods. The integration of predictive technologies and biosensing applications further enriches the utility of LLCs, indicating a promising future for their use in clinical settings. This review points to continued advancements and encourages further research in LLC technology to maximize its therapeutic benefits.

Over 2.2 billion people across the globe face significant barriers to accessing essential ophthalmic care, with elderly, rural, and refugee populations being disproportionately affected. These obsta-cles deepen existing disparities in eye care. 3D printing is a novel technology that has the potential to transform the field and improve access through alleviating many patient-specific barriers. This article delves into the evolution of 3D printing within ophthalmology, highlighting its current ap-plications and future potential. It explores various 3D printing techniques and biomaterials, dis-cussing their effectiveness in creating advanced solutions such as bioengineered corneas, ocular prosthetics, and innovative treatments for dry eye syndrome. Additionally, 3D printing has rev-olutionized drug delivery systems for conditions like glaucoma, retinal diseases, and for ocular brachytherapy. Despite its promise, the integration of 3D printing into clinical practice presents challenges, which the article addresses alongside strategies for overcoming them. By mapping out the technological advancements and challenges, this review offers a roadmap for enhancing global eye care accessibility and improving patient outcomes on a global scale.

Background: Despite a range of available treatments, there is a remaining unmet need for patients with severe post-partum hemorrhage (sPPH). Objective: This manuscript evaluated efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 [NCT04723979], OS-2, OS-3 and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligation, arterial embolization or hysterectomy) and safety (incidence of thromboembolic events [TE] and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa exposed women only. Results: A total of 446 women exposed to rFVIIa and 1,717 non-exposed controls were included. In the RCT, fewer rFVIIa exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio 0.11, 95% confidence interval 0.03–0.35). In OS-1, more rFVIIa exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio 2.46, 95% confidence interval 1.06–5.99). In OS-2, 17% (3/18) of rFVIIa exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio 0.33, 95% confidence interval 0.03–1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa in the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during aerosolization of liquids or powders and the role of aerosol flow dynamics in RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Analyzing existing technical limitations, several potential strategies for enhancing the efficiency of targeted therapeutic delivery to or through the respiratory system are identified and presented, including the use of smart inhaling devices incorporating AI algorithms.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their clinical application has been hindered by their vulnerability to protease degradation and toxicity towards mammalian cells. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs, applicable to effective drug-device combination products. KR12 antimicrobial peptide was chosen and in order to further enhance its delivery and efficacy, HIV TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica nanoparticles with self-entrapped CPP-KR12 peptide using the biomimetic silica precipitability due to its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was delivered at a slightly delayed rate with improved stability against trypsin treatment and a reduction in cytotoxicity over CPP-KR12. Finally, the antimicrobial potential of CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated, which is coated with CPP-KR12 in the form of nanoparticles on the surface of BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug/device combination product for tissue regeneration.

Curcumin, a nontoxic and cheap natural medicine, has high therapeutic efficacy for many diseases including diabetes and cancers. Unfortunately, its exceedingly low water-solubility and rapid degradation in the body severely limit its bioavailability. In this work, we prepare a series of biocompatible poly(vinyl anisole)@nonlinear poly(ethylene glycol) (PVAS@PEG) core-shell nanogels with different PEG gel shell thickness to provide high water solubility, good stability, and controllable sustained release of curcumin. The PVAS nanogel core is designed to attract and store curcumin molecules for high drug loading capacity and the hydrophilic nonlinear PEG gel shell is designed to offer water dispersibility and thermo-responsive drug release. The obtained nanogels are monodispersed in spherical shape with clear core-shell morphology. The size and shell thickness of the nanogels can be easily controlled by changing the core-shell precursor feeding ratios. The optimized PVAS@PEG nanogels display a high curcumin loading capacity of 38.0 wt%. The nanogels can stabilize the curcumin from degradation at pH =7.4 and release the curcumin in response to heat in the physiologically important temperature range. The nanogels can enter cells effectively and exhibit negligible cytotoxicity to both the B16F10 and HL-7702 cells at a concentration up to 2.3 mg/mL. Such designed PVAS@PEG nanogels have a great potential to be used for delicate drug delivery.

Underwater acoustic sensor network (UASN) plays a crucial role in collecting real-time data from remote areas of the ocean. However, deploying the UASN is a challenging problem due to the harsh environment and high deployment cost. Therefore, it is essential to design an appropriate routing protocol to effectively address the issues of routing void, packet delivery delay, and energy utilization. In this paper, an adaptive support-vector-machine-based routing (ASVMR) protocol is proposed for the UASN to prolong the network lifetime and reduce the end-to-end packet delivery delay. The proposed protocol employs a distributed routing approach that dynamically optimizes the routing path in real-time by considering four types of node state information. Moreover, the ASVMR protocol establishes a "routing vector" spanning from the current node to the sink node, and selects a suitable pipe radius according to the packet delivery ratio (PDR). In addition, the ASVMR protocol incorporates future states of sensor nodes into the decision-making process, along with the adoption of a waiting time mechanism and routing void recovery mechanism. Extensive simulation results demonstrate that the proposed ASVMR protocol performs well, in terms of the PDR, the hop count, the end-to-end delay, and the energy efficiency in dynamic underwater environments.

Graphene-based nanomaterials (GNMs), including graphene, graphene oxide, reduced graphene oxide, and graphene quantum dots, may have direct anticancer activity or be used as nanocarri-ers for antitumor drugs. GNMs usually enter tumor cells by endocytosis and can accumulate in lysosomes. This accumulation prevents drugs bound to GNMs from reaching their targets, sup-pressing their anticancer effects. A number of chemical modifications are made to GNMs to facili-tate the separation of anticancer drugs from GNMs at low lysosomal pH and to enable lysosomal escape of drugs. Lysosomal escape may be associated with oxidative stress, permeabilization of the unstable membrane of cancer cell lysosomes, release of lysosomal enzymes into the cytoplasm, and cell death. GNMs can prevent or stimulate tumor cell death by inducing protective autopha-gy or suppressing autolysosomal degradation, respectively. Furthermore, because GNMs prevent bound fluorescent agents from emitting light, their separation in lysosomes may enable tumor cell identification and therapy monitoring. In this review, we explain how the characteristics of the lysosomal microenvironment and the unique features of tumor cell lysosomes can be exploited for GNM-based cancer therapy.

Serial femtosecond crystallography (SFX) using an X-ray free-electron laser (XFEL) enables determination of room-temperature structures without causing radiation damage. Using an optical pump-probe or mix-and-injection, SFX enables the intermediate state visualization of a molecular reaction. In SFX experiments, serial and stable microcrystal delivery to the X-ray interaction point is vital for reasonable data collection and efficient beam time. The Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) facility established SFX instruments at a nanocrystallography and coherent imaging (NCI) experimental station. Various sample delivery methods, including injection, fixed-target scanning, and hybrid methods, have been developed and applied to collect XFEL diffraction data. Herein, we review the currently available sample delivery methods for SFX at the NCI experimental station at the PAL-XFEL. This article will help PAL-XFEL users access the SFX system for their experiments.

Novel pH responsive semi-interpenetrating polymer hydrogels based on tamarind gum-co-poly(acrylamidoglycolic acid) (TMGA) polymers have been synthesized using simple free radical polymerization in the presence of bis[2-(methacryloyloxy)ethyl] phosphate as a crosslinker and potassium persulfate as a initiator. In addition, these hydrogels have been used as templates for green synthesis of silver nanoparticles (13.4±3.6 nm in diameter, TMGA-Ag) by using leaf extract of Teminalia bellirica as reducing agent. Swelling kinetics and equilibrium swelling behavior of the TMGA hydrogels have been investigated in various pH environment the maxium % equilibrium swelling behavior observed i.e., 2882±1.2. The synthesized hydrogels and silver nanocomposites have been characterized by the UV, FTIR, XRD, SEM and TEM. TMGA and TMGA-Ag hydrogels have been investigated to study the characteristics of drug delivery and antimicrobial study. Doxorubicin hydrochloride, a chemotherapeutic agent successfully encapsulated with maximum encapulstaion efficiency i.e., 69.20±1.2 and performed in vitro release studies in pH physiological and gastric environment at 37 ℃. The drug release behavior is examined with kinetic models such as zero order, first order, Higuchi, Hixson Crowell, Korsmeyer-Peppas. These release data was the best fitted with the Korsemeyer-Peppas transport mechanism with n=0.91. Treatment effect on HCT116 Cell, human colon cancer cells were assessed with cell viability and cell cycle analysis. Antimicrobial activity of TMGA-Ag hydrogels is studied against to Staphylococcus aureus and Klebsiella pneumonia. Finally, the results demonstrate that TMGA and TMGA-Ag are promising candidates for anti-cancer drug delivery and inactivation of pathogenic bacteria, respectively.

Cancer is the second biggest cause of death in children. With the development of chemotherapy, there is a substantial increase in overall survival rate over recent 30 years. However, the overall mortality rate in children with cancer still remains 25%, and many survivors experience a decline in overall quality of life and long-term adverse effects caused by treatments. Although cancer cells share common characteristics, pediatric cancers are different from adult cancers in their prevalence, mutation load, and drug response. Therefore, there is an urgent unmet need to develop therapeutic approaches specifically designed for children with cancer. Nanotechnology can potentially overcome the deficiencies of conventional methods of administering chemotherapy and ultimately improve clinical outcomes. The nanoparticle-based drug delivery systems can decrease the toxicity of therapy, provide a sustained or controlled drug release, improve pharmacokinetic properties of loading contents, and achieve a targeted drug delivery with achievable modifications. Further, therapeutic approaches based on combining nanoformulated drugs with novel immunotherapeutic agents are emerging. In this review, we discuss the recently developed nanotechnology-based strategies for treating blood and solid pediatric cancers.

Introduction: OS2966 is a fist-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically-indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for intratumoral, convection-enhanced delivery (CED) of OS2966. Subsequently, patients will undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: 1) the latest CED technology, 2) 2-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active. A Phase I trial is registered at clinicialtrials.gov (NCT04608812).

Inequality of health service for different specialty categories not only occurs in different areas inequality of health service for different specialty categories in the world, but also happens in the online service platform. In the online health community (OHC), health service was often of inequality for different specialty categories, including both online views and medical consultation for offline registered service. Moreover, how the factor city-level impacts the inequality of health service in OHC is still unknown. We designed a causal inference study with data on distributions of serviced patients and online views in over 100 distinct specialty categories on one largest OHC in China. To derive the causal effect of the city-levels (two levels inducing 1 and 0) on the Gini coefficient, we matched the focus cases in cities of rich healthcare resources with the potential control cities. For the Gini coefficient of serviced patients in over 100 specialty categories, the average treatment effect of level-1 cities is 0.470, which is 0.029 higher than that of the matched group. Similarly, for the Gini coefficient of online views, the average treatment effect of Level-1 cities is 0.573, which is 0.016 higher than that of the matched group. For each of the specialty categories, we also estimated the average treatment effect the specialty category’s Gini coefficient ( ) with the balanced covariates. The results support the argument that the total Gini coefficient of all the doctors in OHC shows that the inequality of health service is still very serious. This study contributes to the development of the theoretically grounded understanding of the causal effect of city-level on the inequality of health service in an online to offline healthcare service setting.

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

The manuscript studies the release kinetic of fluorescein from colloidal liquid crystals made up from monoglyceride and different non-ionic surfactants. The release experiments were carried out under sink conditions, and mathematical models were described as extrapolations from solutions of diffusion equation in different initial and boundary conditions imposed by pharmaceutical formulations. The diffusion equation was solved, using Laplace and Fourier transformed functions for the release kinetic from infinite reservoirs in a semi-infinite medium. Solutions represents a general square root law and can be applied for the release kinetic of fluorescein from monoglyceride colloidal liquid crystals. Akaike, Schwartz and Imbimbo criteria were used to establish the appropriate mathematical model and the hierarchy of performances of different models applied to the release experiments. The Fisher statistic test was applied to perform significance of differences among mathematical models. Differences evaluated by mathematical criteria demonstrated that small or no significant statistic differences were carried out between various applied models and colloidal formulations. Phenomenological models were preferred over to empirical and semi-empirical ones. The general square root model shows that the diffusion-controlled release of fluorescein is the mathematical models extrapolated for monoglyceride colloidal liquids, in the first part of the process.

Targeted Protein Silencing (TPS) is an elegant approach to investigate protein function and its role in the cellular landscape, overcoming limitations of genetic perturbation strategies. In contrast to CRISPR/Cas9 and RNA interference, these systems act in a reversible manner and reduce off-target effects. Several TPS have been developed and wisely improved, including compartment delocalization tools and protein degradation systems. In this review, we focus on Anchor-Away, deGradFP, auxin inducible degron (AID) and dTAG technologies, and discuss their recent applications and advances. Finally, we propose Nano-Grad, a novel nanobody-based protein degradation tool to specifically proteolyze endogenous tag-free target protein.

The COVID-19 pandemic has highlighted the critical need for telehealth and remote patient monitoring in healthcare delivery. Despite the growing use of on-body wearable sensors for continuous monitoring and predicting adverse events, such as hospitalizations or falls, their widespread adoption within the healthcare ecosystem remains a significant challenge. While the pandemic has accelerated the acceptance of these technologies, achieving widespread integration requires their sustained incorporation into routine healthcare practices beyond emergency situations. In this study, we extend the application of our previously developed remote patient monitoring system, originally designed for the geriatric frail population, to COVID-19 patients. Our objective is to assess whether the metrics obtained from this system, which includes physical activity and indoor localization sensors, along with vital sign monitoring, can provide additional insights into the recovery trajectory of individuals affected by COVID-19.

The integration of drone technology into healthcare logistics presents a significant opportunity to enhance the speed, reliability, and efficiency of medical sample transportation. This study inves-tigates the current advancements in drone technology, focusing on its application in the rapid and secure delivery of medical samples, particularly in urban and remote regions where traditional transportation methods often face challenges. Utilizing a combination of recent technological de-velopments such as AI-driven navigation systems, real-time monitoring, and secure payload management, the study examines how drones can mitigate logistical barriers like traffic conges-tion and geographical isolation. The research methodology includes a comprehensive review of recent case studies from various regions, illustrating the practical applications and benefits of drones in healthcare. The results demonstrate a substantial reduction in transportation time and costs, along with improved accessibility to healthcare services in underserved areas. The study concludes that, while challenges such as regulatory hurdles and privacy concerns remain, the on-going advancements in drone technology and supportive regulatory frameworks have the poten-tial to revolutionize medical logistics, ultimately improving patient outcomes and healthcare de-livery.

Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment. Being composed of several modules, they offer the advantage of high specificity and biocompatibility in delivering drugs to the target compartment of cancer cells. The large carrier module brings together functioning MNT modules and serves as a platform for drug attachment. The development of smaller-sized MNTs via truncation of the carrier module looks advantageous in facilitating tissue penetration. In this study, two new MNTs with a truncated carrier module containing either an N-terminal (MNTN) or a C-terminal (MNTC) part were developed by genetic engineering. Both new MNTs demonstrated high affinity for target receptors, as revealed by fluorescently labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresis assay, while only MNTN possessed binding to Keap1. Finally, the photodynamic efficacy of the photosensitizer attached to MNTN was significantly higher than when attached to either MNTC or the original MNT. Thus, this work reveals that MNT’s carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1.

Maternal gut and breast milk (BM) are key in vertically transmission bacteria to infants, shaping their gut microbiota in early life. Although the establishment of early gut microbiota is known, the role of the combined influence of maternal factors and newborn characteristics are not explored. In this study we aimed to assess the influence of maternal BMI and total body fat, age, delivery mode, and newborn sex on the diversity and composition of the BM and gut microbiota (GM) in mother- newborn dyads. In this cross-sectional study, of the 986 pregnant women candidates, 53 participated, and finally, 40 mother-newborn dyads exclusively breastfeeding at 20-28 days post-partum were included. Metataxonomic profiling of DNA extracted from BM and fecal samples was conducted using 16S rRNA sequencing. Globally, the findings offer valuable insights that excessive adiposity, age and C-section delivery influence on a lower abundance of specific taxa in the BM, maternal gut, and gut newborns. Also, the simultaneous analysis of maternal factors and newborn characteristics shows that maternal age and newborn sex explain an important variation in the microbiota composition. These results add to understanding of the intricate interplay between maternal factors and the microbial communities that influence early-life gut and BM microbiota.

in the context of advanced nanomaterials research, nanogels have recently gained considerable attention for their versatility and promising biomedical applications. To date, a significant number of nanogels have been developed to meet the growing demands in various fields of biomedical research. Summarising preparation methods, physicochemical and biological properties and recent applications of nanogels may be useful to help exploring new directions for their development. This article presents a comprehensive overview of the latest nanogel synthesis methodologies, highlighting advances in formulation with different types of hydrophilic or amphiphilic polymers. It also underlines recent biomedical applications of nanogels in drug delivery and imaging, with a short section dedicated to biosafety considerations of these innovative nanomaterials. In conclusion, this article summarises recent innovations in nanogel synthesis and their numerous applications, highlighting their considerable potential in the biomedical field.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder that is caused by mutations in the survival motor neuron 1 (SMN1) gene, hindering the production of functional survival motor neuron (SMN) proteins. Antisense oligonucleotides (ASOs), a versatile DNA-like drug, are adept at binding to target RNA to prevent translation or promote alternative splicing. Nusinersen is an FDA-approved ASO for the treatment of SMA. It can effectively promote alternative splicing in SMN2, an analog of SMN1, to produce a greater amount of full length SMN protein, to compensate for the loss of functional protein translated from SMN1. Despite its efficacy in ameliorating SMA symptoms, the cellular uptake of these ASOs is suboptimal and their inability to penetrate the CNS necessitates invasive lumbar punctures. Cell-penetrating peptides (CPPs), that can be conjugated to ASOs, represent a promising approach to improve the efficiency of these treatments for SMA and have the potential to transverse the blood-brain barrier to circumvent the need for intrusive intrathecal injections and their associated adverse effects. This review provides a comprehensive analysis of ASO therapy, their application for the treatment of SMA, and the encouraging potential of CPPs as delivery systems to improve ASO uptake and overall efficiency.

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.

Human Immunodeficiency Virus (HIV) infection and its latent recurrent infection make vaccine development a significant challenge for traditional vaccines; however, the mRNA delivery of multiepitope antigens capable of creating antibodies against the surface proteins of HIV-1 and HIV-2 along with their respective Nef proteins, responsible for the latent infection can bring a most effective, as well as affordable solution to the unresolved epidemics of HIV. In this paper, we present the complete design of a multiepitope vaccine to prevent acute infections and inactivate Nef proteins that block the MHC-1 and MHC-2 pathways to hide the virus for later reinfection.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

Delivery of drugs through the nasal route provides an alternative, yet highly efficacious modality for administering both large and small pharmaceutic molecules. This method proves particularly advantageous for drugs that are unstable during oral administration, as they undergo significant degradation in the gastrointestinal tract or metabolization through the first-pass effect in the liver. Nasal administration stands as a viable alternative to parenteral therapy and is also suitable for long-term medical management. The nasal mucosa, characterized by high vascularity and permeability, facilitates rapid pharmaceutical absorption, ensuring a swift onset of therapeutic action. Despite its noninvasive nature, the nasal delivery technique finds broad applicability for both local treatment and systemic therapy, as the drug directly enters systemic circulation. This article explores the feasibility of a novel spray delivery mechanism for intranasal drug deposition. The study aims to determine whether users can correctly follow the state-of-the-art application instructions for a nasal spray with an optimal nozzle placement angle (namely, 12-15°) at the nostril while maintaining sufficient safety and efficacy, and without engaging in preventable usage errors that could harm the user. Additionally, the study evaluates the effectiveness of device labeling, instructions for use, and a short video in supporting the correct application of the nasal spray at the optimal angle (12-15°) and assesses whether users can differentiate the product from others with similar appearances. We have also performed physical spray tests to experimentally evaluate drug penetration to the nasopharynx (a key target site for viral infections) for two different nozzle placements – one for current package instructions coming with over-the-counter spray products and the other for the optimal spray usage procedure to enhance targeted drug delivery. Human Factors (HF) validation studies were also conducted, instructing users to follow the application instructions of the nasal spray bottle with the nozzle placed at the optimal angle to target the nasopharynx. The experimental tests consistently confirmed improved penetration with the 12-15° nozzle placement, with visual cues proving effective when used in tandem with written instructions for guiding the study participants to adhere to the recommended usage procedures.

Wound infection is a common complication of chronic wounds. It can impair healing, which may not occur without external help. Antimicrobial dressings (AMDs) are a type of external help to infected chronic wounds. In this study, highly porous membranes made of only chitosan and containing the antiseptic polyhexanide (poly(hexamethylene biguanide); PHMB) were prepared by cryogelation, aiming to be used in AMDs. These membranes exhibited high water swelling capacity, fast water absorption and high water vapor transmission. The best drug loading method involved simultaneous loading by soaking in a PHMB solution and sterilization by autoclaving, resulting in sterilized, drug-loaded membranes. The drug release kinetics was comparable to that of a commercial PHMB-releasing AMD assayed under the same conditions. These membranes exhibited high antibacterial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are bacterial species commonly found in infected wounds, and blood clotting activity. The obtained results suggest that these membranes may be suitable for use in the development of AMDs.

Some cancer cells rely heavily on non-essential biomolecules for survival, growth, and proliferation. Enzyme based therapeutics can eliminate these biomolecules, thus specifically targeting neoplastic cells; however, enzyme therapeutics are susceptible to immune clearance, exhibit short half-lives, and require frequent administration. Encapsulation of therapeutic cargo within biocompatible and biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) is a strategy for controlled release. Unfortunately, PLGA NPs exhibit burst release of cargo shortly after delivery or upon introduction to aqueous environments where they decompose via hydrolysis. Here we show the generation of hybrid silica-coated PLGA (SiLGA) NPs as viable drug delivery vehicles exhibiting sub-200 nm diameters, a metastable Zeta potential, and high loading efficiency and content. Compared to uncoated PLGA NPs, SiLGA NPs offer greater retention of enzymatic activity and slow the burst release of cargo. Thus, SiLGA encapsulation of therapeutic enzymes, such as asparaginase, could reduce frequency of administration, increase half-life, and improve efficacy for patients with a range of diseases.

Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of Coronavirus (COVID-19). However, due to the low concentration and fast reaction characteristics of NO in cardiovascular system, the clinical applications centered on the NO delivery are challenging. In this tutorial review, we first summarized the methods to estimate the in vivo NO delivery process based on the clinical images and mathematical modeling to assess the endothelial function and vulnerability of atherosclerotic plaque. Then, the emerging bioimaging technologies that have the potential to directly measure the arterial NO concentration were discussed, including the Raman spectroscopy and electrochemical sensor. Aside from the diagnostic methods, therapies aimed at controlling NO delivery to regulate CVD were reviewed, including the inhaled NO therapy to treat the pulmonary hypertension and COVID-19, stem cell therapy and NO-releasing platform to treat endothelial dysfunction and atherosclerosis.

Nanotechnology is an emerging field of modern science based on the use of nanoparticles (NPs) with a huge potential in many sectors, including nanomedicine. Their small size confers them unique properties because they are subject to physical laws that are in the middle between classical and quantum physics. In this context, NPs project plays a pivotal role because the composition, size, shape and surface proprieties need to be carefully considered for their optimal design and application. As reported in this review, NPs are classified in inorganic (metallic NPs; quantum dots; carbon-based nanostructures; mesoporous silica nanoparticles) and organic (liposomes and micelles, dendrimers and polymer nanoparticles) ones. Here, we report an accurate description of the potential of each NPs type focusing on their multiple areas of application like theranostics drug delivery, imaging, tissue engineering, antimicrobial techniques and nanovaccines, and therefore they represent a promise to revolutionize the new era of nanomedicine, especially in cancer research.

Nanometer-curved surfaces are abundant in biological systems as well as in nano-sized technologies. Properly functionalized polymer-grafted nanoparticles (PGNs) adhere to surfaces with different geometries and curvatures. This work explores some of the energetic and mechanical characteristics of the adhesion of PGNs to surfaces with positive, negative and zero curvatures using Coarse-Grained Molecular Dynamics (CGMD) simulations. Our calculated free energies of binding of the PGN to the curved and flat surfaces as a function of separation distance show that curvature of the surfaces critically impacts the adhesion strength. We find that the flat surface is the most adhesive, and the concave surface is the least adhesive surface. This somewhat counterintuitive finding suggests that while a bare nanoparticle is more likely to adhere to a positively curved surface than a flat surface, grafting polymer chains to the nanoparticle surface inverts this behavior. Moreover, we studied the rheological behavior of PGN upon separation from the flat and curved surfaces under external pulling force. The results presented herein can be exploited in drug delivery and self-assembly applications.

innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan can be used to create biocompatible and biodegradable scaffolds with 3D architectures similar to human structures, allowing their efficient and safe use as tissue engineering and drug delivery systems in chronic wounds. Locally heated tumors above polymer lower critical solution temperature can induce its conversion into a hydrophobic form, enhancing drug release until the thermal stimulus is gone, where a lower release is due to the swelling of the material. This paper integrates the relevant reported contributions of bioengineered scaffolds for thermo-responsive drug delivery in wound healing. Therefore, we present a comprehensive review that aims to demonstrate the capacity of these systems to provide spatially and temporally controlled release strategies for one or more drugs used in wound healing. In this sense, the novel manufacturing techniques of 3D-printing and electrospinning are explored for the tuning of their physicochemical properties to adjust therapies according to the patient’s convenience, as well as reduce drug toxicity and side effects.

Nanotechnology has enabled the development of novel therapeutic strategies such as targeted nanodrug delivery systems, control and stimulus-responsive release mechanisms, and the production of theranostic agents. As a prerequisite for the use of nanoparticles as drug delivery systems, the amount of loaded drug must be precisely quantified, a task for which two approaches are currently used. However, both approaches suffer from the inefficiencies of drug extraction and of the solid-liquid separation process, as well as from dilution errors. This work describes a new, reliable, and simple method for direct drug quantification in polymeric nanoparticles using attenuated total reflection Fourier transform infrared spectroscopy, which can be adapted for a wide variety of drug delivery systems. Silk fibroin nanoparticles and naringenin were used as model polymeric nanoparticle carrier and drug, respectively. The specificity, linearity, detection limit, precision and accuracy of the spectroscopic approach were determined in order to validate the method. A good linear relation was observed within 0.00 to 7.89 % of naringenin relative mass with an R2 of 0.973. The accuracy was determined by the spike and recovery method. Results showed an average 104% recovery. The limit of detection and limit of quantification of the drug loading content were determined to be 0.3 and 1.0 %, respectively. The method's robustness is demonstrated by the notable similarities between the calibrations carried out in two different equipment and institutions.

Background: We assess locoregional drug targeting effectiveness of intraoperative (IO) cryoprobe-assisted injection of blue dye (BD) and cytotoxic-tracer mixture (TTM), in VX2 tumor model, and its translational value to cryo-assisted breast tumor surgery with BD alone. Methods: Under computed tomography (CT) guidance, we injected two ml TTM in five aliquots in the margin of 16 frozen or normothermic VX2 tumors. We evaluated the IO and post-operative drug targeting and therapeutic efficacy in tumor-host interface (T-HI) by CT, gross examination, and histopathology. In twenty-six T1 to T4 primary breast cancer (BRCA) we performed ultrasound-guided (US) cryoprobe-assisted tumor freezing, BD guided lymphatic mapping, and surgery. We evaluated, IO and in freshly resected specimen, BD distribution pattern in T-HI, lymph node(s), breast parenchyma, and resection cavity. Results: Fluids-impervious frozen VX2 or breast tumor transported drug(s) an arc-like pattern at T-HI regardless of freeze dose, number of freeze-thaw cycles, drug dose fractionation, tumor characteristics or dimensions. During melting, TTM spread within fifty percent VX2 tumor mirrored that of T-HI; it was massive in normothermia. In VX2 twenty percent focal margin necrosis at pathology coincided with CT gap; in both studies, BD dose-staining spread in T-HI and tumor was linear. Eighty-four patients had one to twelve stained axillary lymph nodes; sixty-nine percent and all respectively, had another quadrant and resection cavity stained. Conclusion: Intraoperative freezing-assisted drug delivery and targeting techniques during cryoablation of VX2 tumor translate successfully to locoregional BD targeting, lymphatic mapping during cryo-assisted surgery of breast cancer.

Fluid flow in human body is generally known to influence a variety of cellular behaviors. Different nanoparticle properties as well as cell type, interaction with other cells and cellular environments also show significant effect on nanoparticle uptake and drug efficacy. The aim of this study was to evaluate the effect of shear stress on cellular behaviors of biocompatible and biodegradable nanoparticles to cancer cells (A549 cell lines) in a biomimetic microfluidic system. We prepared a gelatin-oleic conjugate (GOC) as an amphiphilic biomaterial to prepare self-assembled gelatin-oleic nanoparticles (GON). Coumarin-6 and paclitaxel were used as the fluorescence marker and model drug, respectively, and were loaded into GONs by incubation (C-GONs; PTX-GONs). Additionally, we evaluated the cellular uptake of fluorescence labeled C-GONs and the drug efficacy of PTX-GONs. The cellular uptake of C-GONs by A549 cells in the absence of shear stress revealed that the mean fluorescence intensity was slightly decreased compared to that in the presence of shear stress. The results also indicated that negatively charged PTX-GONs had a lower cancer killing effect under dynamic conditions than that under static conditions. It also suggested that fluidic shear stress did not significantly affect drug uptake and efficiency in case of PTX-GONs. The cellular interactions between nanoparticles and cells in drug delivery should be carefully examined according to the physicochemical properties of nanoparticles such as the type of materials, size and mainly surface charge in a biomimetic microfluidic condition.

Lately Silicon Carbide (SiC) and Galium Nitride (GaN) based high frequency power conversion has gained immense popularity which stems from relatively low switching energy, robustness to high temperature operation, wide-band gap and superior thermal limits. While this aspect inherently results in a high-density power stage design, the design of adjoining passive components, particularly magnetics, needs careful attention. This is especially true if the compatibility of core and winding options and their performance is limited with the use of higher switching frequency. In this regard, this paper presents a brief review of existent research conducted in materials, optimization and integration of magnetics for single and three phase applications, ranging from filters, resonant inductors to isolation transformers. Design knobs pertaining to medium voltage (MV) applications, low-voltage (LV) applications, e-mobility sector such as more electric aircrafts (MEAs) and electric vehicles (EVs) are discussed. Guidelines for magnetics design are summarized for each application with a projected roadmap on future trend for magnetics.

This study presents a mixed review of research on the competencies of built environment professionals in infrastructure delivery within emerging economies. By integrating bibliometric analysis with a systematic review, the research offers a comprehensive understanding of key themes, trends, and debates in the field. The review process culminated in the selection of 59 publications, which were analyzed to identify critical topics including embedding emerging skills in built environment competencies, competency-based curriculum, technology infrastructure and assessment, municipal competency training, and the role of the Fourth Industrial Revolution (4IR). The findings underscore the importance of evolving educational frameworks to meet the demands of globalization, integrating advanced technologies, and fostering industry-academic collaborations to enhance the skills of professionals in the built environment sector. This approach ensures a robust examination of the competencies necessary for effective infrastructure delivery in emerging economies.

Background: The integration of unmanned aerial vehicles (UAVs), commonly known as drones, into medical logistics offers transformative potential for the transpor-tation of sensitive medical materials, such as blood samples. Traditional car transportation is often hindered by traffic delays, road conditions, and geographic barriers, which can compromise timely delivery. Methods: This study provides a comprehensive analysis comparing high-speed drone transportation with traditional car transportation under various weather conditions. Blood samples, including EDTA whole blood, Serum, Li-Heparin Plasma, and citrate plasma tubes, were transported via both methods across temperatures ranging from 4 to 20 degrees Celsius. The integrity of the samples was assessed using a wide array of analytes and statistical analyses, including Passing-Bablok regression and Bland-Altman plots. Results: The results demonstrated that drone transportation maintains blood sample integrity comparably to traditional car transpor-tation. For serum samples, the correlation coefficients (r) ranged from 0.830 to 1.000, and the slopes varied from 0.913 to 1.111, with minor discrepancies in five analytes (total bilirubin, calcium, ferritin, potassium, and sodium). Similar patterns were observed for EDTA, Lithium-Heparin, and Citrate samples, indicating no significant differences between transportation methods. Conclusions: These findings highlight the potential of drones to enhance the efficiency and reliability of medical sample transport, particularly in scenarios requiring rapid and reliable delivery. Drones could significantly improve logistical operations in healthcare by overcoming traditional transportation challenges.

Oxytocin is recommended as the first-line choice for labor induction in term pregnant women with premature rupture of membranes (PROM); however, it can occasionally lead to failed induction and delivery complications. The primary objective of this study was to compare delivery information and outcomes following the administration of oxytocin infusion or oral low-dose misoprostol solution for labor induction in term PROM women with an unfavorable cervical condition. Methods: A prospective nested case-control study was conducted at a tertiary general hospital in China from March 2020 to February 2024, comparing oxytocin infusion and oral administration of 25ug misoprostol every 2 hours for labor induction in term PROM women with a Bishop score <6. A total of 449 mothers were included, with 282 in the oxytocin group and 167 in the misoprostol group. Results: The rates of vaginal delivery and failed induction were similar between the two groups. The duration of total labor time was shorter in the misoprostol group. There were no significant differences observed regarding the incidence of uterine hyperstimulation, fetal stress, or suspected intrauterine infection between the two groups; however, there was a markedly higher incidence of postpartum hemorrhage (PPH) and severe PPH but lower postpartum urinary retention (PPUR) observed in the oxytocin group. Logistic regression analysis revealed that misoprostol administration demonstrated a negative relationship (aOR: 0.46; 95% CI: 0.21-0 .95) with failed labor induction outcomes, while IVF-ET showed a positive association (aOR:3.12; 95% CI:1.49-6.43). Furthermore, there was a negative correlation identified between misoprostol administration and occurrence of PPH (aOR: 0.49; 95% CI: 0.27-0.85). Conclusions: Oral low-dose misoprostol has demonstrated both safe and superior efficacy to oxytocin infusion for labor induction and may potentially reduce the incidence of failed induction and associated with a decreased risk of PPH were observed in the misoprostol group in term PROM pregnant women with unfavorable cervical condition.

This qualitative study explores the relationship between supply chain responsiveness (SCR) and customer loyalty within the e-commerce sector. E-commerce has revolutionized global commerce, driven by technological advancements and shifting consumer behaviors. Central to e-commerce success is the ability to meet customer expectations swiftly and reliably, necessitating agile supply chain management (SCM) practices. SCR in e-commerce encompasses the capacity to adapt to dynamic market demands, minimize disruptions, and enhance customer satisfaction through efficient logistics, inventory management, and last-mile delivery. Through in-depth interviews with customers, e-commerce platform managers, and supply chain practitioners, this study investigates key themes, challenges, strategies, and impacts associated with SCR and customer loyalty. Findings reveal that customers prioritize fast order fulfillment, reliable service quality, personalized experiences, and trustworthy interactions, all of which significantly influence their loyalty and advocacy behaviors. Challenges identified include inventory management complexities, logistical hurdles in last-mile delivery, and the need for effective supplier communication. Strategic approaches to enhance SCR include leveraging data analytics for demand forecasting, adopting agile SCM practices, integrating customer feedback into service improvements, and fostering collaborative relationships with suppliers. These strategies not only optimize operational efficiency but also cultivate enduring customer relationships based on satisfaction, trust, and loyalty. The study concludes that improved SCR practices lead to increased customer satisfaction, repeat purchases, and positive word-of-mouth, thereby strengthening competitive advantage and sustainability in the e-commerce marketplace.