Microcrystal delivery instruments are pivotal to perform serial femtosecond crystallography experiments at the XFEL facilities. We present a novel sample delivery technique based on a micro-tubing reeling system (MRS). Even though the tiny size of the micro-tubing, the MRS device has an advantage of operation without real-time position adjustment of the tube to match with the XFEL pulses. Moreover, the applicable repetition rate is more flexible than the previously reported chip-based one-dimensional fixed target system.

Glioblastoma (GB), even though not frequent, is an extremely aggressive brain tumor, with a strong impact on patient outcomes, in terms of both length and quality of life. The protocol estab-lished by Stupp and coworkers in 2005, based on radiotherapy and temozolomide chemotherapy, after maximum safe surgical resection, remains the gold standard for GB treatment. However, it is evident nowadays that the extreme GB intratumoral and intertumoral heterogeneity, invasive-ness and recurrence are not compatible with a routinary and unfortunately uneffective treatment. In this review article, we summarize the principal challenging issues in finding new valuable therapies for GB and focus on the impact that extracellular vesicle (EV) research and exploitation can have in the field. EVs are natural particles delimited by a lipidic bilayer and full of functional cellular content, released and uptaken by cells as key means of cell communications. Moreover, being stable in body fluids, well-immunotolerated, able to cross physiological, inter-species, and inter-kingdom barriers, and to target specific cells, releasing inherent or externally loaded functionally active molecules, EVs can be potentially ideal allies in fighting GB and assuring to GB patients a better prognosis. Here we report the main results obtained until now, focusing on both EV sources and molecular cargo used in the different functional studies, mainly in vivo. Finally, we perform a SWOT analysis reporting both the main advantages and the pitfalls of developing EV-based GB therapeutic strategies to highlight the main directions to explore for realizing the promise of EV exploitation for GB treatment.

Cardiovascular disease (CVD) accounts for nearly one-third of all global fatalities, establishing itself as a leading cause of death. To address this pressing issue, there is a growing demand for improved diagnostic methods and secure, non-invasive imaging techniques that can deliver precise insights into the progression of CVD. The success of personalized therapy for CVD depends on a couple of critical factors: accurate diagnosis and early detection. Therapeutic options for conditions like CVD, which develop over several decades, are highly specific to the individual's condition and the stage of the disease. In the field of biomedicine, nanotechnology has become increasingly prominent as a tool with diverse applications, including diagnostics, biosensing, and drug delivery. This review article offers an in-depth look at the most recent developments in the utilization of nanotechnology for detecting and managing prevalent cardiovascular diseases, providing valuable insights into this crucial area of healthcare research.

Chitosan nanoparticle delivery systems have potential for enhancing bone healing and addressing osteomyelitis. The objective was to deliver antimicrobial agents capable of preventing or treating osteomyelitis. Each formulation was optimized to achieve desired characteristics in terms of size (ranging from 100 to 400 nm), PDI (less than 0.5), zeta potential (typically negative), and in vitro release profiles for gentamicin. Entrapment percentages varied with gentamicin ranging from 10% to 65%. The chitosan nanoparticles exhibited substantial antimicrobial efficacy, particularly against both P. aeruginosa and MRSA, with zones of inhibition ranging from 13 to 24 mm and complete reduction in colony forming units observed between 3 to 24 hours. These chitosan nanoparticle formulations loaded with antimicrobials hold promise for addressing orthopedic complications.

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

Curcumin (CUR) is a phytochemical with potent anticancer activities as demonstrated by both preclinical and clinical studies. CUR bioformulations, including loading in biodegradable polymers, have been explored to increase CUR’s solubility and chemical stability, control its release, and improve its delivery to cancer cells. In this study, copolymers comprising poly (L-lactide)-poly (ethylene glycol)-poly (L-lactide) (PLA-PEG-PLA) and poly (ethylene glycol)-poly (L-lactide)-poly (ethylene glycol) (PEG-PLA-PEG) were designed and synthesized to assess and compare their curcumin delivery capacity and inhibitory potency on MCF-7 breast cancer cells. Molecular dynamics simulations indicated that PLA-PEG-PLA has a higher propensity to interact with the cell membrane and more negative free energy, suggesting it is the better carrier for cell membrane penetration. Our characterization indicated that the microsphere copolymers were synthesized successfully. Of the two formulations, PLA-PEG-PLA experimentally exhibited better results, with an initial burst release of 17.5%, followed by a slow, constant release of the encapsulated drug up to 80%. PLA-PEG-PLA-curcumin showed a significant increase in cell death in MCF-7 cancer cells (IC50 = 23.01 ± 0.85 µM) based on the MTT assay. These data were consistent with gene expression studies of Bax, Bcl2, and hTERT which showed that PLA-PEG-PLA-CUR induced apoptosis more efficiently in these cells. Our study integrates in vitro and in silico approaches to identify an optimal co-polymer for the delivery of CUR to cancer cells.

Sepsis is a life-threatening condition caused by a dysregulated host response to an invading pathogen such as multidrug-resistant bacteria. Despite recent advancements, sepsis is a leading cause of morbidity and mortality, resulting in a significant global impact and burden. This condition affects all age groups, with clinical outcomes depending mainly on timely diagnosis and appropriate early therapeutic intervention. Because of the unique features of nanosized systems, there is a growing interest in developing and designing novel solutions. Nanoscale-engineered materials allow a targeted and controlled release of bioactive agents, resulting in improved efficacy with minimal side effects. Additionally, nanoparticle-based sensors provide a quicker and more reliable alternative to conventional diagnostic methods for identifying infection and organ dysfunction. Despite recent advancements, fundamental nanotechnology principles are often presented in technical formats that presuppose advanced chemistry, physics, and engineering knowledge. Consequently, clinicians may not grasp the underlying science, hindering interdisciplinary collaborations and successful translation from bench to bedside. In this review, we abridge some of the most recent and most promising nanotechnology-based solutions for sepsis diagnosis and management using an intelligible format to stimulate a seamless collaboration between engineers, scientists, and clinicians.

The structure of wound dressing materials presents one of the most relevant characteristics for effective skin tissue repair. Electrospinning is a common technique used to produce polymeric fibres that can mimic fibrillar disposition of skin extracellular matrix, favouring cell migration, and thus regeneration of the damaged tissue. Moreover, beads, also known as by-products of electrospinning, have potential as reservoirs for sustained drug release. Processing parameters, such as molecular weight and viscosity of the polymer solution, can affect the desirable morphologies of electrospun films. Thereby, this work had the purpose of producing and characterized electrospun polycaprolactone (PCL) mats loaded with propolis, a popular extract in traditional medicine with potential for skin repair aid. Films with different morphologies were obtained depending on the storage period of the solution prior to the lectrospinning, probably due to the PCL hydrolysis. FTIR analyses of the extract confirmed propolis composition. GPC and viscosity analyses demonstrated that the decrease in molar mass over the storage period was responsible for nanostructure diversity. Propolis acts as a lubricant agent, affecting the spun solutions' viscosity and the thermal properties and hydrophilicity of the films. All films are within the value range of the water vapour transpiration rate of the commercial products. The presence of beads did not affect the propolis release pattern. However, "in vitro" wound healing assay showed that propolis-loaded films composed by beaded fibres increased the cell migration process. Thus, it can be inferred that these films presented the potential for wound dressing application.

The CRISPR-Cas9 system is an emerging therapeutic tool with the potential to correct diverse ge-netic disorders. However, for gene therapy applications an efficient delivery vehicle is required, capable of delivering the CRISPR-Cas9 components into the cytosol of the intended target cell population. Once there, the ribonucleoprotein complex (RNP) can be transported into the nucleus. Lipid nanoparticles (LNP) serve as promising candidates for delivery of CRISPR-Cas9 RNP. These delivery vehicles have been optimized for the delivery of nucleic acids, such as mRNA. Co-delivery of Cas9 encoding mRNA with the accompanying sgRNA leads to translation of the Cas9 protein and formation of the Cas9 RNP inside the cell. Only recently, direct delivery of the CRISPR-Cas9 RNP complexes has been explored, which requires adjustments to the LNP formulation. In this study, the importance of buffer composition and cationic charge during RNP and ssDNA en-trapment in LNP are demonstrated. After optimizing several formulation parameters, LNP were prepared that were colloidally stable in human plasma and efficiently deliver the SpCas9 RNP and ssDNA for HDR-correction in reporter cells. Under optimal formulation conditions, gene knock-out and gene correction efficiencies as high as 80% and 20%, respectively were achieved at nanomolar CRISPR-Cas9 RNP concentrations.

miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors comprise of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

Artificial Intellignece (AI) is a platform lending immense assistance in discovering and developing drugs and thus, various such approaches have been developed with the intent of simplifying and improving biomedical operations such as drug repurposing and drug discovery. In the past decade, AI-based investigation of nanomedicines, as well as non-nanomedicines has reached the clinical level. In semblance with the traditional methods of therapy, nanomedicine therapy is employed at limited doses. The study of a variety of drugs resulted in the conclusion that the effect of each drug is variable for every patient and, evaluating that perfect drug combination manually is a time-consuming as well as an inefficient treatment method. Therefore, the use of AI simplifies and reduces the time consumption in determining the perfect customized drug combination for nano-therapy. The area with the most potential for meeting this reality is to optimize the drug and dosage parameters. It is a universally known fact that cancer is dangerous and unique because of the exacting challenges it poses during treatment and, to achieve a better treatment, the therapeutic effect on each patient must be delineated even if the volume of data generated is massive. The article aims at analyzing the AI technologies that help yield results much quicker, make the analyses simple, and efficient.

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

Tailoring extracellular vesicles (EVs) as targeted drug delivery systems to enhance the therapeutic efficacy showed superior advantage over liposomal therapies. Herein, we developed a novel nanotool for targeting B16.F10 murine melanoma, based on EVs stabilized with Polyethylene glycol (PEG) and loaded with doxorubicin (DOX). Nanosized EVs were efficiently enriched from melanoma cells cultured under metabolic stress by ultrafiltration coupled with size exclusion chromatography (UF-SEC) and characterized by size, morphology, and proteome. To reduce their clearance in vivo, EVs were PEGylated and passively loaded with DOX (PEG-EV-DOX). Our data suggested that the low PEG coverage of EVs might still favor EV surface protein interactions with target proteins from intratumor cells, ensuring their use as “Trojan horses” to deliver DOX to the tumor tissue. Moreover, our results showed a superior antitumor activity of PEG-EV-DOX in B16.F10 murine melanoma models in vitro and in vivo compared to that exerted by clinically applied liposomal DOX in the same tumor model. The PEG-EV-DOX administration in vivo reduced NF-κB activation and increased BAX expression, suggesting better prognosis of EV-based therapy than liposomal DOX treatment. Collectively, our results highlight the promising potential of EVs as optimal tools for systemic delivery of DOX to solid tumors.

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

Hypoxia is the main survival challenge that human beings encounter in high altitudes, it is also the leading cause of Acute Mountain Sickness (AMS). Studies have shown that hypoxia induces a large number of reactive oxygen species (ROS) in AMS patients, and the surge of ROS leads to the reduction of oxygen delivery capacity of erythrocyte, senescence and inflammatory impairment of erythrocyte and vascular endothelial cells to a certain extent. Through depicting a target-pathway network, our study indicates that Compound Danshen Dropping Pills (CDDP), which is one of the best-known traditional Chinese medicine used for the treatment of myocardial ischemic diseases, can improve red blood cell oxygen delivery capacity in AMS patients, alleviate tissue and organ damage, relieve a series of clinical symptoms caused by hypoxia through ROS clearance and related mechanisms. We further elucidate the active ingredients of CDDP targeting ROS related pathway by target-ingredient correspondence analysis. Tanshinone IIA, catechol and some other compounds of CDDP were identified to have certain targeting effect on ROS and ROS dependent pathways. This study provides new understandings of CDDP in clinical application on AMS.

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between the particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.

Recent policy and service provision recommends a woman-centered approach to maternity care and encourages the development of personalized models of clinical assistance. As ethnicity has been recognized as determinant in the risk calculation of some obstetric complication, our aim was to assess costs for birth assistance according to the maternal ethnicities. In a five-year period (2012-16) all women admitted for delivery at the Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario ‘A. Gemelli’ IRCCS, Rome, Italy were investigated. Economic evaluations were performed by using the ‘diagnosis-related group’ (DRG) approach. Cost analysis was completed by including maternal ethnicity, delivery mode and perinatal complications. A total of 18,093 patients were involved in the analysis. An overall care expense of €42.663.481 was calculated. Caucasian was the main ethnicity (90.7%), leaving the minority groups to 9.3%. Vaginal delivery (VD) was the most common mode of delivery in all ethnic clusters, with a global rate of 59.6%. Not including Asiatic women, increased CS rates were recorded in all minority ethnic groups (Maghreb (51.5%) and Afro-Caribbean (47.8%)). A double incidence of complicated VD was observed in the minority groups, primarily among Afro-Caribbean (69.9%), followed by Asiatic (64.1%), Maghreb (63.2%) and Latin-America (62.7%) patients. By logistic regression, Afro-Caribbean delivering women had a significant increased risk of complicated CS among all subgroups. Minority groups (Afro-Caribbean, in particular) increase the health care cost for birth assistance due to higher incidence of adverse perinatal outcomes.

Diatom microalgae are the most outstanding natural source of porous silica. Diatom cell is enclosed in 3-D ordered nanopatterned silica cell wall, called frustule. The unique properties of diatoms frustule, including high specific surface area, thermal stability, biocompatibility, tailorable surface chemistry, make them really promising for biomedical applications. Moreover, diatoms are easy to cultivate in artificial environment and there is a huge availability of diatom frustules as fossil material (diatomite) in several areas of the world. For all these reasons, diatoms are an intriguing alternative to synthetic materials for the development of low-cost drug delivery systems. This review article focuses on the possible use of diatoms derived silica as drug carrier systems. The functionalization strategies of diatom micro-/nanoparticles for improving their biophysical properties, such as cellular internalization and drug loading/release kinetics, are described. In addition, the realization of hybrid diatom-based devices with advanced properties for theranostics and targeted or augmented drug delivery applications, are also discussed.

The refractive index of a liquid serves as a fundamental parameter reflecting its composition, thereby enabling the determination of component concentrations in various fields such as chemical research, food industry, and environmental monitoring. Traditional methods for refractive index (RI) measurement rely on light deflection angles at interfaces between the liquid and a material of known refractive index. In this paper, the authors present a new differential refractometer for highly sensitive measurement of RI differences between two liquid samples. Using a configuration with two cells equipped with flat parallel plates as measuring elements, the instrument facilitates accurate analysis. Namely, the sensor signals from both the solution and the solvent cuvette are generated simultaneously with one laser pulse, reducing the possible fluctuations of the laser radiation intensity. Our evaluation shows the high sensitivity of RI measurements (< 7 · 106), so this differential refractometer can be proposed not only as a high-sensitivity sensing tool that can be used for mobile detection of nanoparticles in solution samples, but also to determine the level of environmental nano-pollution using water (including rain, snow) samples from various natural as well as industrial sources, thus helping to solve some important environmental problems.

In this computational study, we investigate the electronic properties of zigzag graphene nano-parallelograms (GNPs), which are parallelogram-shaped graphene nanoribbons of various widths and lengths, using thermally-assisted-occupation density functional theory (TAO-DFT). Our calculations reveal a monotonic decrease in the singlet-triplet energy gap as the GNP length increases. The GNPs possess singlet ground states for all the cases examined. With the increase of GNP length, the vertical ionization potential and fundamental gap decrease monotonically, while the vertical electron affinity increases monotonically. Besides, as the GNP length increases, the symmetrized von Neumann entropy increases monotonically, denoting an increase in the degree of multi-reference character associated with ground-state GNPs. The occupation numbers and real-space representation of active orbitals indicate that there is a transition from the nonradical nature of the shorter GNPs to the increasing polyradical nature of the longer GNPs. In addition, the edge/corner localization of active orbitals is found for the wider and longer GNPs.

In the field of clinical medicine, the real-time monitoring of carbon dioxide gas exhaled by the human body is of great significance. At present, the detection devices in the market are mainly detected by sucking a small amount of gas in the nasal cavity to the detection device, and there are some problems such as too long sampling tubes, easy blockage or distortion, and abnormal gas dispersion. In this paper, a micro-nano optical fiber sensor that can directly detect the concentration of end-tidal carbon dioxide is proposed. The measurement is achieved by using the principle of high evanescent field absorption, and the operating band is 2.004 μm. The sensor uses micro-nano optical fiber as the sensing area, and then detects the presence of carbon dioxide gas exhaled by human body through optical power attenuation. The function of micro-nano fiber is to realize the transmission of signal light and also serve as the absorption medium of the gas to be measured. In addition, the variation of light power also reflects the respiratory cycle of the human body. The sensor can realize rapid real-time response to carbon dioxide gas detection, with small size, low cost, and easy to replace. It has great application potential in clinical scenarios such as Gastrointestinal Endoscopes that require real-time monitoring of human respiration.

In order to effectively utilize red mud, an aluminum industrial waste, the stabilized soil material was developed using nano-SiO2 synergistically modified red mud, and the strength characteristics of the stabilized soil were analyzed to clarify the feasibility of such stabilized soil serves as a road base material. Through different combination schemes, the effects of different nano-SiO2 and cement contents on the strength of the stabilized materials were explored. The test results show that: in the synergistic modification of nano-SiO2 and cement, nano-SiO2 can significantly improve the early unconfined compressive strength of red mud-based stabilized soil; in the synergistic modification of nano-SiO2, gypsum and cement, the 7-d unconfined compressive strength of red mud-based stabilized soil is greater than 2 MPa, which meets the strength requirements of road base materials and shows the superiority of synergism. The nominal stress-strain curves are divided into five stages: compressed and compacted stage, elastic deformation stage, plastic deformation stage, damage deformation stage and residual deformation stage. The macroscopic compressive damage pattern of the specimens shows that the modified red mud-based stabilized soil mostly exhibits brittle damage.

In order to effectively utilize red mud and reduce its occupation of land resources as well as its impact on the environment, experiments were conducted to develop stabilized soil materials using nano-SiO2 synergistically modified red mud and to investigate the curing mechanism of stabilized soil. The unconfined compressive strength, microscopic morphology and curing mechanism of the red mud-based stabilized soil materials with different amounts of modified materials were investigated. The test results show that after 7-days curing, the unconfined compressive strength of red mud-based stabilized soil meets the compressive strength requirement of road base material when nano-SiO2, gypsum and cement are synergistically modified. In such case, the soil structure has the lowest fracture rate and the best structural compactness when the amount of nano-SiO2 is 1%; It is found that the needle-like and columnar calcium alumina in the modified red mud-based stabilized soil increases, and the binding energy of hydration product ions in the modified material is improved; The chemical curing mechanism of modified red mud-based stabilized soil includes hydration reaction, volcanic ash reaction, promotion effect of nano-SiO2, and enhancement effect of gypsum. On this base, a model of early start hydration process of red mud-based stabilized soil promoted by nano-SiO2 is established.

In recent years, graphene has received so much attention because of its superlative properties and its potential to revolutionize electronics especially in VLSI. This study analyzes the effect of single event upset (SEU) in SRAM cell which employs metal-oxide semiconductor type graphene nano-ribbon field effect transistor (MOS-GNRFET) and compares the results respectively with another SRAM cell designed in PTM 10nm FinFET node. Our simulation show there is a change in data stored in the SRAM after heavy ion strike. However, it recovers from radiation effects after 0.46 ns for GNRFET and 0.51 ns for FinFET. Since the degradation observed in Q and Qb of GNRFET SRAM are 2.7X and 2.16X as compared to PTM nano-MOSFET, we can conclude that GNRFET is less robust to single effect upset. In addition, the stability of SRAM can be improved by increasing the supply voltage VDD.

A novel drive current model covering the effects of source/drain voltage (VDS) and gate voltage (VGS) and incorporating drift and diffusion current on the surface channel at the nano-node level, especially beyond 28nm node is presented. The effect of the diffusion current added is more satisfactory to describe the behavior of the drive current in nano-node MOSFETs, fabricated with the atomic-layer-deposition (ALD) technology. This breakthrough in model establishment can expose the long and short channel devices together. Introducing the variables of VDS and VGS, the mixed current model more effectively and meaningfully demonstrates the drive current of MOSFETs under the operation of horizontal, vertical, or mixed electrical field. In comparison between the simulation and experimental consequences, the electrical performance is impressive. The error between both is less than 1%, better than the empirical adjustment to issue a set of drive current models.

In this paper, the far field and near field optical responses of a gold nanoparticle are studied and simulated numerically. The electromagnetic field was excited by an electric dipole located near one end of the nanorod, which is used to model the emission of a quantum dot. Another excitation method was also simulated in which an incident plane wave is used. The excitation of dark plasmon modes of the gold nanorod is presented. The Poynting equation was solved numerically to study the influence of the gold nanorod on the dipole radiative power. In addition, the extinction cross section of the gold nanoparticle illuminated by the incident plane wave was calculated to estimate the amount of the scattered and absorbed light.

This paper presents an overview of the principal structural and dynamics characteristics of reverse micelles (RMs) in order to highlight their structural flexibility and versatility, along with the possibility to modulate their parameters in a controlled-manner. The multifunctionality in a large range of different scientific fields is exemplified in two distinct directions: a theoretical model for mimicry of biological microenvironment and practical application in the field of nanotechnology and nano-based sensors. RMs represents a convenient experimental approach that limits the drawbacks of the conventionally biological studies in vitro, while the particular structure confers them the status of simplified mimics of cells by reproducing a complex supramolecular organization in an artificial system. The biological relevance of RMs is discussed in some particular cases referring to the confinement and crowding environment, molecular dynamics of water and cell membrane structure. The use of RMs in different range of applications seems to be more promising due to their structural and compositional flexibility, a high efficiency and selectivity being achieved. The advance in nanotechnology is based on developing new methods of nanomaterials synthesis and deposition. This review highlighting the advantages of using RMs in synthesis of nanoparticles with specific properties and in nano (bio)sensors design.

Poly(vinylidene fluoride) nanocomposites processed with different morphologies, such as porous and non-porous films and fibres, have been prepared with silica nanoparticles (SiNPs) of varying diameter (17, 100, 160 and 300 nm) which in turn have encapsulated perylenediimide (PDI), a fluorescent molecule. Structural, morphological, optical, thermal, and mechanical properties of the nanocomposites, with SiNP filler concentration up to 16 wt% were evaluated. Further, cytotoxicity and cell proliferation studies were performed. All SiNPs are negatively charged independently of the pH and more stable from pH 5 upwards. The SiNPs introduction within the polymer matrix increases the contact angle independently of the nanoparticle diameters and the smallest ones (17 nm) improve the PVDF Young modulus from 0.94 ± 0.04 GPa for the pristine polymer film to 1.05 ± 0.06 GPa. Varying filler diameter, physico-chemical, thermal and mechanical properties of the polymer matrix were not significantly affected. Finally, the SiNPs inclusion does not induce cytotoxicity in murine myoblasts (C2C12) after 72 h of contact and proliferation studies reveal that the prepared composites represent a suitable platform for tissue engineering applications, as they allow to combine the biocompatibility and piezoelectricity of the polymer with the possible functionalization and drug encapsulation and release of the SiNP.

Hybrid inorganic-polymer nanocomposites can be employed in diverse applications due to the potential combination of desired properties from both the organic and inorganic components. The use of novel bottom-up in situ synthesis methods for the fabrication of these nanocomposites is advantageous compared to top-down ex situ mixing methods, as it offers increased control over the structure and properties of the material. In this review, the focus will be on the application of the sol-gel process for the synthesis of inorganic oxide nanoparticles in epoxy and polysiloxane matrices. The effect of the synthesis conditions and the reactants used on the inorganic structures formed, the interactions between the polymer chains and the inorganic nanoparticles, and the resulting properties of the nanocomposites are appraised from several studies over the last two decades. Lastly, alternative in situ techniques and the applications of various polymer-inorganic oxide nanocomposites are briefly discussed.

Recent progress in the fabricating flexible electronics has been developed significantly due to the increased interest of the flexible electronics which can be applied to enormous fields not only to conventional electronic devices but to bio/eco electronic devices. Flexible electronics can be applied to wide range of fields such as flexible display, flexible power storage, flexible solar cells, wearable electronics and healthcare monitoring devices. Recently, flexible electronics are being attached on the skin and even implanted into human body to monitor the bio-signals and for treatment purpose. To improve the electrical characteristic and the mechanical properties of flexible electronics, nanoscale fabrications using novel nano-materials are required. Advanced in nanoscale fabrication methods allow construction of the active materials that can combine with the ultra-thin soft substrate to form flexible electronics with high performances and reliability. In this review, wide range of nanoscale fabrication methods for flexible electronics classified in either top-down or bottom-up approaches such as conventional photolithography, soft lithography, nanoimprint lithography, growth, assembly and chemical vapor deposition(CVD) will be reported with specific fabrication processes and results. Here, our aim is to introduce various fabrication methods that can be used to fabricate the flexible electronics.

The loss or dysfunction of skeletal tissue often necessitates surgical intervention, particularly in cases involving trauma, tumors, or abnormal development leading to critical-sized defects. Despite autografts being considered the gold standard for bone grafts, their limitations and complications prompt the exploration of alternative approaches for bone repair and regeneration. Current advancements in bone tissue engineering have led to innovative strategies aiming to regenerate injured bone structures, providing viable alternatives to traditional autografts or allografts. Among these strategies, Hydrogel Microparticles (HMPs) have emerged as promising scaffolds due to their notable characteristics, including high porosity and mechanical tunability. HMPs play an important role in facilitating vasculature formation, mineral deposition, and overall bone tissue regeneration. HMPs, fabricated through various techniques, exhibit versatility in functions such as drug and cell delivery, structural scaffolding, and bioinks for 3D printing. In addition, these microgels can be injected for minimally invasive delivery and can display modular properties with different designs and configurations. This review exclusively focuses on the advancements in HMPs for bone regeneration, delving into synthesis and functionalization techniques while highlighting their diverse applications documented in the literature. Our aim is to shed light on the unique benefits and potential of HMPs in the intricate field of engineering bone tissue.

The use of New-age (Nano) Modified Emulsions (NME) for the stabilisation of marginal materials for use in the upper-pavement layers of roads have been proven in laboratories, through Accelerated Pavement Tests (APT) and in practice. In addition, material design methods have been developed based on the scientific analysis of granular material mineralogy and the chemical interaction with the binder to design a material compatible NME stabilising agent for naturally available (often marginal) materials. However, the introduction of any new disruptive technology in a traditionally well-established industry, such as the road construction industry, is usually associated with considerable resistance. This is especially relevant when the new technology enables the use of granular materials traditionally considered to be of an unacceptable quality in combination with relatively new concepts such as New-age (Nano) Modified Emulsions (NME). In practice, few road construction projects are without any problems. The introduction of new-technologies obviously makes it an easy target to blame for any non-related problem that may arise during construction. This article aims to assist in pre-empting, recognising, preventing and resolving material or non-material related construction problems through the correct identification of the cause of the problem and recommending the best, most cost-effective way to correct any deficiencies on site.

Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), and nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in tumor tissues and cause damage to nearby normal tissues. This study describes a targeted cancer therapy approach that uses AS1411 aptamer-conjugated nanospheres, 100-300 nm in size, loaded with doxorubicin (Dox) to selectively identify tumor cells overexpressing nucleolin (NCL) proteins. The study demonstrates that the active target model, which employs aptamer-mediated drug delivery, is more effective than nonspecific enhanced permeability and maintenance (EPR)-mediated delivery and passive drug delivery in improving drug penetration and maintenance in tumor cells. Additionally, the study shows the potential for anticancer effects through 3D spheroidal and in vivo GBM xenograft models. The DNA-protein hybrid nanospheres utilized in this study offer numerous benefits, such as efficient synthesis, structural stability, high drug loading, dye labelling, biocompatibility, and biodegradability. When combined with nanospheres, the 1411 aptamer has been shown to be an effective drug delivery carrier for precisely targeting tumors. This combination has the potential to produce anti-tumor effects in active targeted therapy of GBM.

The last 20 years have seen significant advancements in polymeric drug delivery methods. A formulation or a system that makes it possible for a medicinal ingredient to be injected into the body is known as polymeric drug delivery1. The key choice for many novel medication delivery methods is made achievable by biodegradable and bio-reducible polymers. The research's prospects for practical applications have necessitated the field's development—the choice for a lot of new drug delivery systems. The prospects of the research for practical applications are required for the development in the field. Polymeric drug delivery methods have been developed from natural polymers like arginine, chitosan2, dextrin, polysaccharides, poly (glycolic acid), poly (lactic acid), and hyaluronic acid. Regarding polymeric drug delivery1, synthetic polymers such as poly(2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide), poly(ethylenimine), dendritic polymers, biodegradable, and bioabsorbable polymers have all been considered. Polymeric drug delivery has also been addressed by focusing on drug-free macromolecular therapies, biomimetic and bio-related polymeric systems, and targeting polymeric drug delivery. Pharmaceutical fields are seeing a tremendous rise in the development of polymeric drug delivery methods based on natural and manmade polymers. The successful advancements in the utilization of biocompatible and bio-related copolymers and dendrimers in cancer treatment, including their application as vehicle systems for highly effective anticancer medications3. A new paradigm for the development of polymeric drug and gene delivery systems will be possible through the fusion of viewpoints from the synthetic and biological domains.

The practical application of a pH-responsive Nanoparticle Drug Delivery System (NDDS) in cancer treatment is often hampered by several issues such as the protection of therapeutic molecules from external stresses, inefficient targeted delivery, sustained drug release, and poor efficacy. This study presents an effective design strategy for the synthesis of a pH-sensitive controlled hydrophobic drug delivery method based on the formulation of chitosan (CS)-coated mesoporous silica nanoparticles (MSNs) through the sol-gel method, where hydrolysis takes place in the acidic medium followed by polycondensation of the hydrolyzed products. For this purpose, NH2 modified-MSNs were prepared by using tetraethyl orthosilicate (TEOS) as precursor and cetyltrimethylammonium bromide (CTAB) as a template, and 3-aminopropyltriethoxysilane (APTES) for amine modification, followed by hydrophobic drug loading and CS coating of various concentrations. Camptothecin (CPT) was used as a model drug. Fabricated monodispersed functionalized nanoparticles had sizes ranging from 200nm to 245nm with an encapsulation efficiency as high as 90%. The highest encapsulation efficiency was found for 1% CS coating, which released 50% drug in 120h at pH 6.4 and 20% at pH 7.4 respectively. These nanoformulations exhibited pH-responsive release patterns of CPT under two different pH values (pH=7.4 and pH=6.4). These results contribute to the optimization of NDDS, with potential implications for nanoformulations designed for controlled and sustained drug release particularly to tumors without affecting healthy cells owing to differences in the pH of the tumor microenvironment and the normal physiological environment of cells.

Hearing loss stands as the most prevalent sensory deficit among humans, posing a significant global health challenge. Projections indicate that by 2050, approximately 10% of the world's population will grapple with disabling hearing impairment. While approximately half of these cases have a genetic etiology, traditional interventions such as hearing aids and cochlear implants do not completely restore normal hearing. The absence of biological treatment has prompted significant efforts in recent years, with a strong focus on gene therapy to address hereditary hearing loss. Although several studies have exhibited promising recovery of common forms of genetic deafness in mouse models, existing challenges must be overcome to make gene therapy applicable in the near future. Herein, we summarize the primary gene therapy strategies employed over past years, provide an overview of the recent achievements in the preclinical studies for genetic hearing loss, and outline the current key obstacles to cochlear gene therapy.

For women giving birth, every moment of delay in receiving skilled care significantly increases the risks of stillbirth, neonatal and maternal death. More than half of all births in developing countries including South Africa, take place outside a health facility and without skilled birth attendants. This has therefore, made it difficult to achieve the Sustainable Development Goals of global reduction in maternal mortality, which is a key health challenge globally, especially in developing countries and sub-Saharan Africa in particular. The aim of this study was to explore and describe the views of pregnant women regarding facility-based delivery. Focus group discussions were used to gather information from the pregnant women. Information was collected from six groups of pregnant women who had delivered babies at the antenatal care facilities in the past years. Results showed several factors associated with the failure to use institutional delivery service, such as long distance from the health care facility, lack of transport, lack of transport fare, shortages of skilled staff, failure to disclose pregnancy, cultural and religious beliefs, and staff attitudes.

Drug delivery systems consist of cyclodextrins (CyDs) have kept constant attention for good compatibility, negligible toxicity, and improved pharmacokinetics of drugs. The unique hollow structure has endowed a lot of functions, such as inclusion of guest molecules, functional modification of active hydroxyl groups, and noncovalent interactions. Besides, the polyhydroxy structure has further extended the functions of CyDs by inter/intramolecular interactions and chemical modification. Furthermore, the versatile functions of the complex contribute to physicochemical characteristics alteration of the drugs, therapeutic talent, stimulus-responsive switch, self-assemble capability, and fiber formation. This review attempts to list the recent progress of CyDs and discuss their roles in the drug delivery system. Future perspectives of the construction of CyD-based drug delivery systems are also discussed at the end of this review, which may be the possible directions for the construction of more rational and cost-effective delivery vehicles.

In recent years, functional fluidic electrohydrodynamic (EHD) pumps have attracted considerable attention due to their remarkable features, such as simple structure, quiet operation, and energy-efficient utilization. EHD liquid pumps can be used in various industrial applications, like flow transfer, thermal management, and actuator drive. In this paper, the author reviewed EHD liquid pump research in these specific aspects: the first observation of the EHD effect, its mathematical modeling, and the choice of pump structure, electrode configuration, and working medium. Based on the review, a summary of the development and latest research on EHD pumps can be provided for the readers.

Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg PE, DSPC, cholesterol, and DSPE-PEG-2000, and the mean size of the RTL was in the range of 114 to 133 nm, as measured by NTA. The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly used chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three i.v. injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone.

The most effective method of treating allergic diseases, aimed not at relieving symptoms, but at eliminating the cause of the disease, is allergen-specific immunotherapy (AIT). To reduce the risk of side effects and improve the delivery of allergens to the mucosa, various delivery systems, such as liposomes, dendrimers, nanoparticles, etc., can be used. To date, there are data on the creation of delivery systems based on glycyrrhizic acid (GA) and its derivatives, but such a delivery system has not been used for allergen-specific therapy until now. At the same time, it is known that GA has an anti-inflammatory effect, shifts the balance towards Th1, and increases the number of Treg cells, which means that in the future it can enhance the anti-allergic effect of AIT and reduce the risk of unwanted side effects. Thus, the study of the immunomodulatory effect of supramolecular complexes (micelles) of GA with extracts of allergens seems to be very promising for the development of new drugs for AIT.

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

Background: We previously developed a refined, tumor selective adenovirus, Ad5NULL-A20, har-boring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20mer peptide (A20) in the fiber knob for selective infection via αvβ6 integrin, a marker of aggressive epithelial cancers. Methods: To ascertain the selectivity of Ad5NULL-A20 for αvβ6 positive tumor cell lines of pancreatic and breast cancer origin, we performed reporter gene and cell viability assays. Biodistribution of viral vectors in mice harboring xenografts with low, medium, and high αvβ6 levels was quantified by qPCR for viral genomes 48 hours post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an αvβ6 selective manner, whilst cell killing me-diated by oncolytic Ad5NULL-A20 was αvβ6 selective. Biodistribution analysis following intrave-nous administration into mice bearing breast cancer xenografts demonstrated that Ad5NULL-A20 resulted in significantly reduced liver accumulation coupled with increased tumor accumulation compared to Ad5 in all three models, with tumor: liver ratios improved as a function of αvβ6 expression. Conclusions: Ad5NULL-A20 based virotherapies efficiently target αvβ6 integrin positive tumors following intravenous administration, validating the potential of Ad5NULL-A20 for systemic ap-plications, enabling tumor selective overexpression of virally encoded therapeutic transgenes.

Cancer is one of the health concerns in modern societies. The application of nanotechnology in medical sciences has created new possibilities for the diagnosis, imaging and the treatment of tumors in humans. The present article reviews the application of marine-based gold nanoparticles in diagnosing and treating cancer. The main data were collected from research article on the application of different marine-based gold nanoparticles in detecting and imaging cancer cells as well as in drug delivery system in treatment of cancer. Chitosan is the most used marine natural compound used to fabricate gold nanocomposites and the most reported application of this type of nano-composites is related to drug delivery system. Despite the excellent anticancer potential of different marine natural products, less studies have been conducted on the use of their compositions with gold nanoparticles in cancer therapy than other materials. Moreover, most reports available in this filed are related to their application as a drug delivery system not anticancer drug. In general, there are still challenges and limitations to the use of nanoparticles in medicine, it is hoped that in the near future nanoparticles will create a dramatic revolution not only in oncology but also in medicine.

This review will explore the four major pillars required for design and development of an saRNA vaccine: antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). In will report on the major innovations, preclinical and clinical data reported in the last five years and will discuss future prospects.

Currently 7.6% of the U.S. young adults aged 18-24 years old currently use e-cigarettes. This study piloted three methods of ENDS cessation by measuring cessation rates, motivational techniques that contributed to cessation success, and participants’ changes after decreasing vape use. Participants were randomized into three study arms [nicotine replacement therapy (NRT) + behavioral support, vape-taper + behavioral support, self-guided] in a 1:1:1 ratio. All participants were invited to attend 9 in-person or phone appointments over the 6 month study period. At 12 weeks, 3 of 7 (42.9%) participants in the NRT + behavioral support arm, 6 of 8 (75%) vape-taper + behavioral support arm, and 7 of 9 (77.8%) self-guided arm self-reported being vape- and nicotine-free. At 6 months, 3 of 7 (42.9%) participants in the NRT + behavioral support arm, 6 of 8 (75%) vape-taper + behavioral support arm, 4 of 9 (44.4%) self-guided arm self-reported being vape- and nicotine-free. A challenge to quitting and remain quit is social pressures, but participants identified self-control and establishing new habits to be the best methods to overcome the desire to vape. Participants who received behavioral support and a vape-taper plan from pharmacists were more likely to be vape- and nicotine-free at 6 months.

DevOps is an emerging practice to be followed in the Software Development life cycle. The name DevOps indicates that it’s an integration of the Development and Operation team. It is followed to integrate the various stages of the development cycle. DevOps is an extended version of the existing Agile method. DevOps aims at continuous integration, Continuous Delivery, Continuous Improvement, faster feedback and security. This paper reviews the building blocks of DevOps, challenges in adopting DevOps, Models to improve DevOps practices and Future works on DevOps

Biologic scaffolds have become an attractive approach for repairing the infarcted myocardium and have been shown to facilitate constructive remodeling in injured tissues. This study aimed to investigate the possible utilization of bacterial cellulose membrane patch containing cocultured cells to limit the myocardium's post-infarction pathology. Myocardial infarction was induced by ligating the left anterior descending coronary artery in 45 Wistar rats, and patches with or without cells were attached to the hearts. After one week, the animals underwent echocardiography for assessing ejection fraction and left ventricular end-diastolic and end-systolic volumes. Following the patch formation, cocultured cells retained viability of >90% over 14 days in culture. The patch was applied to the myocardial surface of the infarcted area after staying 14 days in culture. Interestingly, the bacterial cellulose membrane without cellular treatment showed higher preservation of cardiac dimensions; however, we did not observe improvement in the left ventricular ejection fraction of this group compared to coculture treated membranes. Our results demonstrated an important role for bacterial cellulose in supporting cells known to produce cardioprotective soluble factors and may thus provide effective future therapeutic outcomes for patients suffering from ischemic heart disease.

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

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

This research work examined the various communication media used in the rural areas for the purpose of conveying messages to Adolescents in the selected communities in Obio/Akpor Local Government Area of Rivers State, Nigeria - Woji, Rumuigbo, Rumuola, Rumuokwuta and Elelenwo communities. The Taro Yammane Statistical formula for determination of sample size was used in drawing a sample of 363 respondents from a population of 3,630 Adolescents. The simple random sampling method was used in the distribution of the questionnaire to target respondents in the selected communities. Two hundred and eighty two (282) copies of the questionnaire were returned valid, and data from them was analysed and interpreted with the use of frequency tables and percentages. The result shows that traditional communication media is still relevant in the dissemination of information to rural dwellers in general and to Adolescents in particular. The agencies that make use of these media are; village authority, age groups, etc. The research work recommend among others that the government and rural dwellers should hold our traditional and cultural values in high esteem through the use of these media, harmonizing the use of traditional communication media and modern media for effective rural information service delivery.

Chitosan is a cationic polysaccharide usually obtained by alkaline deacetylation of chitin poly(N-acetylglucosamine). It is biocompatible, biodegradable, mucoadhesive and non-toxic. These excellent biological properties make chitosan a good candidate for a platform in developing drug delivery systems having improved biodistribution, increased specificity and sensitivity, and reduced pharmacological toxicity. In particular, chitosan nanoparticles are found to be appropriate for non-invasive routes of drug administration: oral, nasal, pulmonary and ocular routes. These applications are facilitated by the absorption-enhancing effect of chitosan. Many procedures for obtaining chitosan nanoparticles have been proposed. Particularly, the introduction of hydrophobic moieties into chitosan molecules by grafting to generate a hydrophobic-hydrophilic balance promoting self-assembly is a current and appealing approach. The grafting agent can be a hydrophobic moiety forming micelles that can entrap lipophilic drugs or it can be the drug itself. Another suitable way to generate self-assembled chitosan nanoparticles is through the formation of polyelectrolyte complexes with polyanions. This paper reviews the main approaches for preparing chitosan nanoparticles by self-assembly through both procedures and illustrates the state of the art of their application in drug delivery.

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

Nanocellulose is cellulose in the form of nanostructures, i.e. features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, e.g. in bacterial cellulose; nanofibers, e.g. in electrospun matrices; nanowhiskers and nanocrystals. These structures can be further assembled into bigger 2D and 3D nano-, micro- and macro-structures, such as nanoplatelets, membranes, films, microparticles and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluonacetobacter), plants (trees, shrubs, herbs), algae (Cladophora) and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology and biomedical applications, e.g. for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.

Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

The application of dry lubrication in rolling contacts is challenging due to wear. In previous studies graphene platelets applied as dry lubricants on the surfaces of angular contact ball bearings demonstrated superior properties. These specific bearings, experiencing both rolling and spinning motion, create more severe conditions for dry lubricants. The applied graphene platelets have a thickness of few graphene layers in the nm range and a diameter in the µm range. Such platelets can be produced by mechanical exfoliation from graphite. To delve deeper into the lubrication effects, investigations were carried out using a milli tribometer. In the tests, a fixed steel ball is sliding against an oscillating counterpart under defined load. During the measurements, the applied load and tangential forces on the ball are recorded to calculate the friction. In our case, a steel ball with a diameter of 6 mm was used against graphene-based films on flat bearing surfaces (axial bearing washer). Comparative investigations included nano graphite particles and fullerene as dry lubricants, in addition to graphene platelets of various staple thicknesses. To increase the adhesion of the films to the surfaces, a pre-rolling process was implemented. Afterwards, the friction on the compressed films was measured. The results indicate that the pre-rolling process effectively reduces the friction of the system. After testing, the surfaces underwent analysis using laser scanning microscopy to assess the formed films, wear, and material transfer. It has been demonstrated that the pre-rolling process leads to the formation of a very thin compacted film with surface protective properties. On the ball as counterpart, the graphene platelets generate a transfer film on the contacting surface.

Soil salinity is seen as a major restriction for crop production, and with water scarcity this problem becomes more complicated. Mulching is crucial to salinity dynamics management by decreasing evaporation with improving the soil’s characteristics. Using chitosan as an eco-friendly biostimulant can enhance plant defense genes during different abiotic stresses. Recently, agricultural research has recognized nanoparticles as a pioneer material due to their distinctive physicochemical features. Therefore, a lysimeter experiment was conducted to investigate the interactive effects of mulching (UNM: un-mulched, WPM: white plastic, RSM: rice straw and SDM: sawdust) and chitosan foliar application (Ch0: control, Ch1: 250 mg chitosan L-1, Ch2: 125 mg nano chitosan L-1, and Ch3: 62.5 mg nano chitosan L-1) on the biochemical soil characteristics and common beans productivity under salt affected soil conditions. Organic mulching (RSM and SDM) treatments significantly improved the soil's organic carbon, available nutrient content, and total count of bacteria. WPM treatment lowered soil EC to 6.63 dS m-1 and increased soil water content to 34.13%. The application of Ch3 caused considerable increases in the plant height, shoot dry weight, root dry weight, grain yield, and nutrient content in the seed. The total fungi count in the soil and Na% in the seed was significantly decreased due to chitosan foliar applications. Moreover, the interactive effect of different mulch materials plus foliar by chitosan applications gave a statistically similar seed yield in both seasons. Overall, this study revealed the potential of the mulching treatments and foliar application of nano chitosan in improved biochemical soil characteristics and common bean productivity under saline soil conditions.

In this paper we introduce the concept of Nano Beta Closure, Nano Beta Interior and study the relationship between them also study some of their properties. Based on these notions we introduced the topological Approach to Decision Making and Its Application in the Medical Field" which describes the use of topological methods in decision-making, specifically through the utilization of nano beta closure and nano beta interior. These mathematical tools are applied in the medical field to improve diagnostic accuracy and aid in treatment planning. The authors demonstrate the effectiveness of this approach through a case study on the diagnosis of Chronic Kidney. The results show that the topological approach using nano beta closure and nano beta interior provides a reliable and accurate method for medical decision-making. Finally, we introduce a medical application for disease groups patients of with chronic kidney. To identify the main causative agent of kidney disease. where using this approach, the medical team can identify the specific areas of the kidney that are affected by the infection, as well as the extent of damage and any potential complications. This information is used to create an individualized treatment strategy that is customized to meet the specific requirements of the patient. and medical history. We write an algorithm that can be a helpful tool for doctors to utilize in diagnosing infection disease Chronic Kidney infections. By utilizing this approach, clinicians can provide accurate diagnoses, develop effective treatment plans, and ultimately improve patient outcomes. finally, we show that fractals hold significant importance in future nano topological generation of the human factor. Their unique properties and self-similar patterns offer insights into the complex organization of biological systems and provide a foundation for designing advanced Nanosystems.

Diabetes mellitus is a cluster of metabolic diseases characterized by hyperglycemia. Since this epidemic growing worldwide, the usage of phototherapeutics to manage diabetes is vital. Coccinia grandis (Aka ivy gourd) belongs to cucumber family is identified as a most effective herb, especially for diabetes and many other disease conditions. Hence, an instant herbal porridge cube incorporating Coccinia grandis leaf powder was produced and sensory acceptability of the porridge was evaluated using trained panelists. The bioactive activity of Coccinia grandis leaf powder showed that 66.77±0.74 mg/g GAE of Total Phenolic Content, 27.65±6.79% of DPPH radical scavenging activity, 5.72% of alpha-amylase inhibition activity and 59.64% of alpha-glucosidase inhibition activity. The effect on postprandial blood sugar levels after consuming the developed porridge was measured using healthy adults and it was observed there was no blood sugar elevation during the 2 hours of time. As a further development, Coccinia grandis leaf extract was nano-encapsulated with food grade Sodium alginate and it was incorporated into the same porridge as a safe delivery method of bioactive compounds. In-vitro digestion assay was conducted and the results show that alpha-amylase inhibition activity for the gastric phase and alpha-glucosidase inhibition activity for the intestinal phase was higher in nano-encapsulated porridge. The study concludes that, consuming nano-encapsulated Coccinia grandis leaf extract with porridge is more beneficial for diabetic patients.

Organophilic nano clay is the composition of mostly clay and organic molecules designed to improve various materials' physical and chemical properties. Permanent deformation in asphalt pavements is primarily the result of inadequate compaction, excessive loading, and high temperatures. Rutting can result in aquaplaning, leading to accidents and costly maintenance and rehabilitation works that drain the economy. Such behavior of asphalt pavements may be attributable to poor selection of aggregate, asphalt binder, or substandard asphalt binders. This study used different percentages of organophilic nano clay ranging from 3.0% - 5.0% with two penetration grade bitumen, i.e., N.R.L 60-70 &amp; N.R.L 80-100. Adding organophilic nano clay to asphalt binder significantly reduced the rutting potential under cyclic loading at high temperatures (55 °C). Ten modified formulations and two virgin bitumen specimens were prepared. The modified binders' viscosity and rutting were tested using the Rotational Viscometer and Wheel Tracker Test (W.T.T.), respectively. The results were analyzed using software for Statistical Analysis. It was recorded that organophilic nano clay-modified bitumen significantly affected rutting to interpret the results. The results indicated that rutting decreased and viscosity increased in all nano clay-modified bitumen samples, with a 4.5% O.N.C modified binder showing the most significant improvement.

The present work is focused on functionalizing Montmorillonite (Mt) with poly dimethyl siloxane (PDMS) to develop a hybrid membrane reactor for the removal of Co (II) and Ni (II) ions from model wastewater samples. The specific surface area of the novel material was found to be 444 m2 /g. X-Ray Diffraction (XRD) and Fourier Transform Infra-Red (FTIR) spectra reveal the formation of exfoliated composite material. The efficiency of this membrane material was determined by subjecting it to continuous filtration experiments. It was able to remove 50% of Co (II) and 75% of Ni (II) ions, respectively, in one cycle of filtration in less than three minutes of operation with a permeate flux rate of 675 L/m2/H and 975 L/m2/H respectively, for both the ions.

This work presents the production and incorporation of calcium hydrolyzed nano-solutions at three concentrations (1, 2, and 3 wt.%) in alkali-activated gold mine tailings (MTs) from Arequipa, Perú. A first activator solution of sodium hydroxide (NaOH) at 10M was used. The calcium hy-drolyzed nano-solutions acted as a secondary activator and as additional calcium resource for the alkali-activated materials (AAMs) based on the low-calcium gold MTs. High-resolution trans-mission electron microscopy/energy-dispersive x-ray spectroscopy (HR-TEM/EDS) analyses were carried out to characterize the morphology, size, and structures of the calcium hydrolyzed na-noparticles. Fourier transform infrared (FTIR) analyses then were used to understand the chemical bonding interactions in the calcium hydrolyzed nanoparticles and in the AAMs. Scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS) and Quantitative X-ray diffraction (QXRD) were performed to study the structural, chemical, and phase compositions of the AAMs; uniaxial compressive tests evaluated the compressive strength of the reacted AAMs; and Nitrogen adsorption-desorption analyses measured the porosity changes at nanostructure level in the AAMs. The results indicate that each increase in the concentration of the calcium hydrolyzed nano-solution had a direct/proportional effect on the mechanical properties of the AAMs samples. The AAMs with 3 wt.% calcium-hydrolyzed nano-solution had the highest compressive strength value of 15.16 MPa, which represented an increase of 62% compared to the original system without nanoparticles and aged under the same conditions of 70°C for seven days. These results provide useful information about the positive effect of calcium-hydrolyzed nanoparticles on gold MTs and their conversion into sustainable building materials through alkali activation.

Of course, now we know that quantum mechanics has been a fundamental structure of our world since our universe came into being. However, it has been only a century since the experimental and theoretical discovery of quantum mechanics and its extensions into many implications and applications. In particular, there are implications across many disciplines that most likely will affect education, health, security, etc. Examples are given of the need for starting education as early as possible in schools, the use of nano-robots to deliver drugs targeted to specific molecular sites, to developing new cryptographic systems to safeguard our privacy.

The size of TiO2 (either nanometric or micrometric) can significantly affect both its photocatalytic and photoelectrochemical properties, thus altering the photooxidation of organic pollutants in air or water. The purpose of this work is to give an account of the photoelectrochemical and photocatalytic features of some nano- and micro-sized TiO2 commercial powders towards a model reaction, the photooxidation of acetone. Cyclic voltammograms (CV) of TiO2 particulated electrodes under UV illumination experiments were carried out in either saturated O2 or N2 solutions for a direct correlation with the photocatalytic process. In addition, the effect of different reaction conditions on the photocatalytic efficiency under UV light in both aqueous and gaseous phases was also investigated. CV curves with the addition of acetone under UV light showed a negative shift of the photocurrent onset, confirming the efficient transfer of photoproduced reactive oxygen species (ROSs), e.g., hydroxyl radicals, or holes to acetone molecules. The photocatalytic experiments showed that the two nano-sized samples exhibit the best photocatalytic performance. The different photoactivity of the micro-sized samples is probably attributed to their morphological differences, affecting both the amount and distribution of free ROSs involved in the photooxidation reaction.

Evaporation studies of water using classical molecular dynamics simulations are largely limited due to its high computational expense. We aim at addressing the computational issues by developing a coarse grain model for evaporation of water on solid surfaces by combining four water molecules into a single bead. Most commonly used mono atomic pair potentials like Lennard Jones, Morse, Mie and three body potential like Stillinger-Weber are optimized using a combination of Genetic algorithm and Nelder-Mead algorithm. Among them, Stillinger-Weber based model shows excellent agreement of density and Enthalpy of vaporization with experimental results for a wide range of temperatures. Further, the new water model is used to simulate contact angle of water and thin film evaporation from surfaces with different wettabilities.

Amorphous ferrite-type rare-earth (RE) substituted garnets and garnet-oxide nanocomposite layers are prepared on clear glass substrates by using RF magnetron sputter-deposition process. By using a combination approach employing custom-built spectrum-fitting software in conjunction with Swanepoel’s envelope method, the spectral dispersion function of optical constants and the layer thicknesses are derived accurately from the transmission spectra of the as-deposited samples. The effects of excess metal-oxides added to the base material systems during the co-deposition process are found to affect the refractive index and the optical absorption coefficients of garnet-oxide composites. A number of optical constant datasets are presented, enabling the experimentalists to design nanophotonic or integrated-optics devices employing these functional materials.

Aiming at the damage detection and continuous monitoring of high efficiency composite structure, the method of carbon nano sensor embeded in the 3-D braided composite material specimen was put forward and the method of damage location for 3-D braided composite material was described. In this paper, the mechanical and electrical characteristics of carbon nano-fiber were analyzed. Considering the massive data of the health monitoring of composite processing, to ensure that the system has good real-time performance, quaternary matrix Singular Value Decomposition algorithm is proposed to simplify data and improve the efficiency of the algorithm. The existence of injury is determined and the damage location is calculated by comparing with key features of healthy specimen. Experimental results prove the method is feasible and effective.

A new class of nano-cube core-shell heterostructures containing Ag coating on the top of WO₃ was fabricated. Physical vapor deposition was used to produce WO₃ based nano-heterostructures. All kind of wet toxic chemical process was avoided to make the process simple and contaminant free. Sputtering of WO₃ and a subsequent thermal annealing process was done to create nano-cubes of WO₃. After that, sputtering of Ag was performed to form the Ag-WO₃ core-shell nano-heterostructures (CSNH). The CSNHs were characterized using field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), X-ray diffraction analysis (XRD) and UV-vis spectroscopy. The morphologies, elemental analysis, interfaces, crystallinity, phases, and chemical compositions were analyzed. The bottom-up growth of WO₃ nanocubes was studied using different time periods at 900°C. Ag coating was also studied before and after annealing. Finally, an optical property (band gap) was also analyzed using Tauc plot derive from absorption spectra. The tailoring the band gap of WO₃ from ~2.9eV to ~ 2.45 eV was observed while Ag-WO₃ CSNH formed.

Opportunistic networks, an evolution of mobile Ad Hoc networks (MANETs), offer decentralized communication without relying on preinstalled infrastructure, enabling nodes to route packets through different mobile nodes dynamically. However, due to the absence of complete paths and rapidly changing connectivity, routing in opportunistic networks presents unique challenges. This paper proposes a novel probabilistic routing model for opportunistic networks, leveraging nodes' meeting probabilities to route packets towards their destinations. The model dynamically builds routes based on the likelihood of encountering the destination node, considering factors such as last meeting time and acknowledgment tables to manage network overload. Additionally, an efficient message detection scheme is introduced to alleviate high overhead by selectively deleting messages from buffers during congestion. Furthermore, the proposed model incorporates cross-layer optimization techniques, integrating optimization strategies across multiple protocol layers to maximize energy efficiency, adaptability, and message delivery reliability. Through extensive simulations, the effectiveness of the proposed model is demonstrated, showing improved message delivery probability while maintaining reasonable overhead and latency. This research contributes to the advancement of opportunistic networks, particularly in enhancing connectivity and efficiency for Internet of Things (IoT) applications deployed in challenging environments.

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

The active form of fingolimod (FTY720; FT) is a sphingosine-1-phosphate receptor agonist with potential ocular applications. The goal of the present study was to develop an FT-loaded nanoemulsion (NE; FT-NE) formulation for the efficient and prolonged delivery of FT to the posterior segment of the eye through the topical route. FT-NE formulations were prepared with homogenization followed by probe sonication method. The lead FT-NE formulation (0.15% and 0.3% w/v loading), comprising soybean oil as lipid and Tween® 80 and Poloxamer 188 as surfactants, was further evaluated for in vitro release, surface morphology, filtration sterilization, and stability at refrigerated temperature. The formulation, at both dose levels, showed desirable physicochemical characteristics, a nearly spherical shape with homogenous nanometric size distribution, and was stable for 180 days (last time point checked) at refrigerated temperature post-filtration through polyethersulfone (0.22 µm) membrane. In vitro release studies showed prolonged release, compared with the control FT solution (FT-S), over 24 h. The results from these studies demonstrate that the FT-NE formulation can serve as a viable platform for the ocular delivery of FT through the topical route.

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

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

Over the few decades, cancer-associated mortalities and morbidities were continuously increased worldwide despite sophisticated technological advancements. Pharmaceutical interventions associated with drugs exhibit a high degree of side effects and toxicities in addition to very high costs. Subsequently, to reduce or to vanish the side effects and high costs, researchers are now exploring natural bioactive compounds such as quercetin in its nanoformulations along with biologics as cargo delivery vehicles. Quercetin along with mesenchymal stromal lineage-derived extracellular vesicles (EVs) possesses an anti-cancer potential that can be explored to treat hepatocellular carcinoma (HCC). Exerting enhanced effect, nano quercetin synergistically with EVs triggers the anti-cancer mechanisms by regulating and dysregulating several signalling mechanisms including NF-κB, p53, JAK/STAT, MAPK, Wnt/β-catenin and PI3K/AKT, in addition to PBX3/ERK1/2/CDK2, and miRNAs modulation. In addition, findings regarding the potential checkpoints of anti-cancer signalling pathways were investigated that offer opportunities to develop engineered EVs incorporated with nano quercetin for the development of novel therapeutics to treat HCC in future. In this present mechanistic review, we abridged the regulation of such signalling mechanisms synergetic approach of nano quercetin and EVs. The regulatory role of EVs in the manifestation of innumerable miRNAs has also been tailed with special context to HCC.

Oral vaccines are highly envisaged for veterinary applications due to their convenience and ability to induce protective mucosal immunity as the first line of defense. The present investigation harnessed live-attenuated Salmonella Typhimurium to orally deliver novel expression vector systems containing the Cap and Rep genes from porcine circovirus type 2 (PCV2), a significant swine pathogen. The antigen expression by the vaccine candidates JOL2885 and JOL2886, comprising eukaryotic pJHL204 and pro-eukaryotic expression pJHL270 plasmids respectively, was confirmed by western blot and IFA. We evaluated their immunogenicity and protective efficacy through oral vaccination in a mouse model. This approach elicited both mucosal and systemic immunity against PCV2d. Oral administration of the candidates induced PCV2-specific sIgA, serum IgG antibodies, and neutralizing antibodies, resulting in reduced viral loads in the livers and lungs of PCV2d-challenged mice. T-lymphocyte proliferation and flow-cytometry assays confirmed enhanced cellular immune responses after oral inoculation. The synchronized elicitation of both Th1 and Th2 responses was also confirmed by enhanced expression of TNF-α, IFN-γ, IL-4, MHC-I, and MHC-II. Our findings highlight the effectiveness and safety of the constructs with an engineered-attenuated S. Typhimurium, suggesting its potential application as an oral PCV2 vaccine candidate.

The COVID-19 pandemic, which has affected the entire world, has not only created a number of emerging issues for each country, especially in the field of public health, but has also provided a number of opportunities for risk management, alternative strategies and completely new ways of looking at challenges. This paper examines the COVID-19 pandemic response in Türkiye and the possible implications of the experience for future responses to other health emergencies and disaster risk management, based on the lessons learned. This study uses publicly available literature from government, private sector, and academic sources to analyse the conflicts, changes and lessons learned during the COVID-19 pandemic, which are components of the World Health Organization (WHO) Health Emergency and Disaster Risk Management (Health EDRM) framework. The COVID-19 experience in Türkiye has several aspects, including the significant role of healthcare workers, the existence of an effective health system accustomed to emergencies, applications based on information technologies, partial transparency of public authorities in providing information, and socio-cultural environment related to cooperation on prevention strategies, including wearing masks and vaccination. Challenges in Türkiye include distance learning in schools, lockdowns that particularly affect the elderly, ensuring environmental sustainability, hesitation about the effectiveness of social/financial support programmes, socio-cultural trivialisation of pandemics after a while, and relaxation of prevention strategies. Lessons learned from the COVID-19 pandemic include the value of transparency in public health/healthcare information, the strengthening of all aspects of the health system in terms of health workers, and the importance of a balanced economy prepared for foreseeable risks.

Apigenin (API) possesses excellent antitumor properties, but its limited water solubility and low bioavailability restrict its therapeutic impact. Thus, a suitable delivery systems is needed to overcome these limitations and improve the therapeutic efficiency. Poly (lactic-co-glycolic acid) (PLGA) is a copolymer extensively utilized in drug delivery. Hyaluronic acid (HA) is a major extracellular matrix and can specifically bind with CD44 on colon cancer cells. Chitosan (CS) can serve as an intermediate binding with HA and PLGA. Herein, we aimed to perpare receptor-selective HA-coated PLGA nanoparticles (NPs) for colon cancer with high expression of CD44. Firstly, API was encapsulated in PLGA to obtain PLGA-API-NPs, which were then sequentially combined with CS and HA to form HA-coated PLGA NPs. HA coated PLGA NPs had a stronger sustained-release capability. Cellular uptake of HA coated PLGA NPs was enhanced in HT-29 cells with high expression of CD44. HA-PLGA-DiR-NPs can target specificity towards the HT-29 ectopic tumor model. Overall, HA coated PLGA NPs was an effectively drug deliver platform for API in treatment of colon cancer with high expression of CD44.

The number of people affected by eye conditions is growing every year, due to the popularity of electronic devices and an aging population. In the world of medicine, accomplishing eye medication administration has always been a difficult task. Despite the fact that there are many eye drops on the market, most of them have important limitations due to quick clearance mechanisms and ocular barriers. One solution with tremendous potential is the contact lens used as medication delivery vehicle to bypass this constraint. Therapeutic contact lenses for ocular medication delivery have attracted a lot of attention because they have the potential to improve ocular bioavailability, patient compliance, and reduce side effects. However, it is essential not to compromise essential features such as water content, optical transparency, and modulus in order to target successful in vitro and in vivo sustained drug delivery profile from impregnated contact lenses. Aside from difficulties like drug stability and burst release, the changing of lens physical and chemical properties caused by therapeutic or non-therapeutic components can limit the commercialization potential of pharmaceutical-loaded lenses. Research has progressed towards bioinspired techniques and smart materials to improve the efficacy of drug-eluting contact lenses. The bioinspired method uses bioinspired polymeric materials to improve biocompatibility, a specialized molecule recognition technique called molecular imprinting, or a stimuli-responsive system to improve biocompatibility and support drug delivery efficacy of drug-eluting contact lenses. This review encompasses strategies of material design, lens manufacturing and drug impregnation under the current auspices in ophthalmic therapies and projects an outlook onto future opportunities in the field of eye conditions management by means of active principles-eluting contact lens.

Hydrogels prepared from natural polymer have attracted extensive attentions in biomedical fields such as drug delivery, wound healing, and regenerative medicine due to their good biocompatibility, degradability and flexibility. This review outlines the commonly used natural polymer in hydrogel preparation, including cellulose, chitosan, collagen/gelatin, alginate, hyaluronic acid and starch. The polymeric structure and process/synthesis of natural polymers are illustrated, and natural polymer-based hydrogels including the hydrogel formation and properties are elaborated. Subsequently, the biomedical application of hydrogels based on natural polymer in drug delivery, tissue regeneration, wound healing and other biomedical field is summarized. Finally, the future perspectives of natural polymers and hydrogels based on them are discussed. For natural polymer, novel technologies such as enzymatic and biological methods are developed to improve the structural properties and the development of new natural based polymers or natural polymer derivatives with high performance is still very important and challenging. For natural polymer-based hydrogels, novel hydrogel materials, like double-network hydrogel, multifunctional composite hydrogels and hydrogel microrobots are designed to meet the advanced requirements in biomedical application, and new strategies such as dual-crosslinking, microfluidic chip, micropatterning and 3D/4D bioprinting, have been explored to fabricate advanced hydrogel materials with designed properties for biomedical application. Overall, natural polymeric hydrogels have attracted increasing interests in biomedical application, and the development of novel natural polymer-based materials and new strategies/methods for hydrogel fabrication is badly desirable and still challenging.

In this work, alkylammonium-functionalized hollow mesoporous silica as nonocarrier of drugs was synthesized to realize enhanced cancer therapy by pH stimuli for sustained drug release. First, functionalized hollow mesoporous silica nanoparticles (Hollow MSNs) were synthesized using dodecyl dimethyl(3-sulfopropyl)ammonium hydroxide (DDAPS), sodium dodecyl sulfate (SDS), and triethanolamine as structure-directing agents, and tetraethyl orthosilicate (TEOS) and N-trimethoxysilypropyl-N,N,N-trimethylammonium chloride (TMAPS) as silica sources under basic condition via the sol-gel process. The structure and morphology of the alkylammonium-functionalized hollow mesoporous silica nanoparticles (Hollow MSN-N+CH3) were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption-desorption analysis, and Fourier-transform infrared (FT-IR) spectroscopy. The functionalized hollow MSNs had a particle size of about 450 nm and a shell thickness of about 60 nm with uniform size. The nanoparticle had a surface area of 408 m2g-1, pore volume of 0.8 cm3g-1 and a uniform pore diameter of 45.9 Å. In the cancer cell viability test with MCF-7 cell, fludarabine-incorporated and alkylammonium-functionalized hollow mesoporous silica nanoparticles (Flu/Hollow MSN-N+CH3) showed excellent cancer cell death comparable with pure fludarabine drug with the controlled drug release by pH stimuli. It is considered that our current materials have the potential applicability as pH-responsive nanocarriers in the field of cancer therapy.

Microfluidic technology has become a powerful tool for several applications in chemistry, physics, biology, and engineering. Benefiting from the advantages of flowing fluids in the laminar regime, droplet-based microfluidics enable the development of various delivery systems based on food-grade emulsions, such as multiple emulsions, microgels, microcapsules, solid lipid micro-particles, and giant liposomes. Besides, by manipulating fluids on a micrometer scale with low-energy demand, it is possible to control the size, shape, and dispersity of droplets generated, which makes microfluidic emulsification an excellent strategy to modulate delivery system properties depending on the entrapped compound type. Thus, this review points out the most current advances in droplet-based microfluidic processes, in which food-grade materials were successfully utilized to develop simple and complex delivery systems. In that context, we sum-marized the principles of droplet-based microfluidics, introducing the most common microde-vices geometries, manufacturing materials, and forces involved in the different droplet generation processes within the microchannels. Subsequently, the encapsulated compound type, classified as lipophilic or hydrophilic functional compounds, was used as a starting point to present current advances in delivery systems based on food-grade emulsions and assembly using microfluidic technologies. Finally, we discuss the limitations and perspectives of scale-up in droplet-based microfluidic approaches, including the challenges that have limited the transition of microfluidic processes from lab-scale to industrial-scale.

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

Development of bioresponsive extrudable hydrogels for 3D bioprinting is imperative to address the growing demand for scaffold design and efficient and reliable methods of tissue engineering and regenerative medicine. This study proposed genipin-crosslinked gelatin-hyaluronic acid hydrogel bioink with different amounts of gelatin tailored for 3D bioprinting, focusing on high cell density loading and less artificial extra-cellular matrix (ECM) effect, as well as exploring their potential applications in tissue engineering. The bioresponsiveness of these hydrogel scaffolds was successfully evaluated in different physiological conditions. 3D and four-axis printing of complex structures such as shapes of hollow tube, star, pyramid, and four-axis tubular scaffolds prove the hydrogel’s high extrusion ability and post-printing shape fidelity. Cytocompatibility and high cell density 3D bioprinting using this moderately stable hydrogel exhibit high potential for precise cell-delivery modes in tissue engineering as well as regenerative medicine.

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

The supramolecular based macrocyclic amphiphiles have attracted great attention in the field of drug delivery due to their unique self-assembling nature. Therefore, these macrocycles are used as nanocarriers for the delivery of poor water soluble drugs, and also for those which have lower permeability, and cannot cross the barrier to reach the desired site. Herein, we design and synthesized a new supramolecular amphiphilic macrocycle to overcome these problems. The macrocycle was synthesized in two steps. In first step 4-hydroxybenzaldehyde was treated with 1-bromotetradecane to obtain a derivatized product which was then treated with resorcinol to cyclize and get calix(4)resorcinarene based supramolecular amphiphilic macrocycle. The synthesized macrocycle and intermediate products were characterized by Mass spectrometry, IR and 1H-NMR spectroscopic techniques. The amphiphile was screened for biocompatibility studies, vesicles formation, and then Amphotericin-B was loaded in the supramolecular amphiphile based vesicles and was characterized for shape, size, homogeneity, surface charge, drug entrapment, in-vitro release profile and stability through atomic force microscopy (AFM), Zetasizer, HPLC and FT-IR. Amp-B loaded macrocycle based vesicles were investigated for in-vivo bioavailability in rabbits. The synthesized macrocycle was nontoxic in cancer cells, hemo-compatible and safe in mice. The drug-loaded macrocycle based vesicles appeared spherical, nano-ranged, and homogeneous in size with negative surface charge and were able to load an increased amount of drug. The vesicles are stable upon storage and when incubated with gastric simulated fluid. Amp-B increased oral bioavailability was achieved when delivered in synthesized macrocycle based vesicles. These results point out that the synthesized supramolecular amphiphile is an efficient nanocarrier to enhance the oral bioavailability of lipophilic drugs

Nanomaterials such as pH-responsive polymers are promising for targeted drug delivery systems, due to the difference in pH between tumor and healthy regions. However, there is a significant concern about the application of these materials in this field due to their low mechanical resistance, which can be mitigated by combining these polymers with mechanically resistant inorganic materials such as mesoporous silica nanoparticles (MSN) and hydroxyapatite (HA). Mesoporous silica has interesting properties such as high surface area and hydroxyapatite has been widely studied to aid in bone regeneration, providing special properties adding multifunctionality to the system. Furthermore, fields of medicine involving luminescent elements such as rare earth are an interesting option in cancer treatment. The present work aims to obtain a pH-sensitive hybrid system based on silica and hydroxyapatite with photoluminescent and magnetic properties. The nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), nitrogen adsorption methods, CHN elemental analysis, Zeta Potential, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), vibrational sample magnetometry (VSM), and photoluminescence analysis. Incorporation and release studies of the antitumor drug doxorubicin were performed to evaluate the potential use of these systems in targeted drug delivery. The results showed the luminescent and magnetic properties of the materials and showed suitable characteristics for application in the release of pH-sensitive drugs.

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

Rottlerin(R) is a natural extract from Mallotus philippensis with antiviral properties. Feline Infectious Peritonitis (FIP) is a fatal disease characterized by systemic granulomatous inflammation and high mortality, with no established prevention or cure. We investigated antiviral effect of liposome loaded R, Rottlerin-liposome(RL) against Feline infectious peritonitis virus (FIPV), the causative agent. We demonstrated that R and RL inhibited FIPV replication in dose dependently with a PKCδ related manner, not only in the early endocytosis step but also in the late step of replication. RL resolved the low solubility issue of rottlerin and improved its inhibition efficacy at the cellular level. Based on these findings, we suggest that RL has a value for further research as a potential antiviral agent against FIPV.

Hydrogel microneedles are a promising technology for the delivery of different types of medicines locally and painlessly, as well as ISF extraction. As the hydrogel microneedles are inserted into the tissue, they swell and release drugs. To improve the effectiveness of this technology in delivering medicine at controlled and desirable doses and intervals, a deep understanding of the mechanism of drug delivery inside the microneedles is required. In this work, drug diffusion inside a tapered microneedle is investigated using numerical simulation. The microneedle is divided into many small elements, and the mass transfer equation of meloxicam is solved in each element over time. The skin is simulated as the sink in the microneedle surface for drug absorption. Simulations are performed for different sizes of microneedles. For a microneedle with a height of 500 µm and a base diameter of 250 µm, the drug completely penetrates the skin within 3.2 seconds. The rate of drug diffusion from the tip of the microneedle is higher than diffusion from the side area near the microneedle base. The obtained data demonstrate that in addition to the height and the base diameter, the microneedle’s aspect ratio, h/d, also affects the time of drug diffusion. We present a nonlinear equation to predict the time of complete drug diffusion as a function of the microneedle geometrical parameter, including the height and base diameter. The proposed equation calculates the total drug diffusion time with an error of less than 7% for all studied cases. Predicting drug diffusion patterns inside microneedles can be helpful in the biomedical field, especially in the drug-controlled release system for the optimization of drug delivery.

Nanomedicine holds great potential to devise better drug delivery systems (DDSs). However, many reported nanomedicines still fall short of commercial requirements including specific targetability, scale-up manufacturing and safety. Cell/tissue based carriers, including cell membrane vehicle and exosome, are biocompatible and targeting platforms but usually suffered from low yields and unstable reproducibility. Here in this study, we proposed the concept and preparation of reconstituted lipid nanoparticles (rLNPs) to develop highly reproducible cell/tissue based lipid nanoparticles (LNPs) for drug delivery, which holds the potential as a versatile drug delivery platform. The whole lipids of cell or tissue were firstly extracted and then prepared into rLNPs using solvent diffusion method. In this way, the preparation of ultra-small (~20 nm) rLNPs can be easily applied to both cell (mouse breast cancer cell line, 4T1) and tissue (mouse liver tissue). Our results demonstrated that mouse liver tissue derived rLNPs can be further labeled/modified with imaging, targeting or other functional moieties. Furthermore, rLNPs were highly biocompatible and capable of loading different drugs including doxorubicin hydrochloride (Dox) and curcumin (Cur). Most importantly, Dox loaded rLNPs (rLNPs/Dox) showed preferable in vitro and in vivo anticancer performance. Therefore, rLNPs might be a versatile drug delivery platform for future application in the treatment of a variety of diseases.

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer; presents novel nanomedicine therapeutics aimed to improve the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for clinical application of nanomedicine in management of LC resistance.

There are various biomaterials in nature, but none fulfills all the requirements. Cellulose, eco-friendly material-based biopolymers, have been advanced biomedicine to satisfy most market demand and circumvent many ecological concerns. This review aims to present an overview of the state of the art in cellulose's knowledge and technical biomedical applications. It included an extensive bibliography of recent research findings for fundamental and applied investigations. The chemical structure of cellulose allows modifications and simple conjugation with several materials, including nanoparticles, without tedious efforts. Cellulose-based materials were used for biomedicine applications such as antibacterial agents, antifouling, wound healing, drug delivery, tissue engineering, and bone regeneration. They advanced the applications to be cheap, biocompatible, biodegradable, easy for shaping and processing into different forms, with suitable chemical, mechanical and physical properties.

Molecularly imprinted polymers (MIPs) have been widely used in nanomedicine during the last few years. However, their potential is limited by their intrinsic properties resulting, for instance, in lack of control in drug release processes or complex detection for in vivo imaging. Recent attempts in creating hybrid nanomaterials combining MIPs with inorganic nanomaterials succeeded in providing a wide range of new interesting properties suitable for nanomedicine. Through this review, we aim to illustrate how hybrids molecularly imprinted polymers may improve patient care with enhanced imaging, treatments and combination of both.

Galangin(Gal) is a natural active flavonoid compound separated from the roots and rhizomes of Alpinia ofcinarum Hance. Modern pharmacological studies have shown that Gal has a variety of biological activities such as anti-tumor, anti-fungal, anti-bacterial, anti-inflammatory, anti-ischemic stroke, suppressing vitiligo and Alzheimer’s disease, etc. The purpose of this research was to prepare a galangin self-microemulsion drug delivery system (Gal-SMEDDS) and compare its anti-oxidant activity and pharmacokinetics with free Gal.The average particle size of the prepared Gal-SMEDDS was approximately 21.33 nm, the polydispersity index was 0.096, the zeta potential was -4.09 mV, and the entrapment efficiency was 96.74%. Compared with free Gal, the release of Gal-SMEDDS was improved in vitro release experiment. Cell experiments showed that Gal had obvious anti-oxidation effect, and the effect of Gal-SMEDDS was better than that of free Gal. In vivo pharmacokinetic experiments showed that the pharmacokinetic parameters of Gal-SMEDDS were better than that of free Gal, which indicated that the self-microemulsion drug delivery system(SMEDDS) effectively increases the oral bioavailability of Gal and alters its pharmacokinetic parameters, such that it may be effective in the treatment of anti-oxidant.

Hydrogels obtained from the combination of different polymers are an interesting strategy for the development of controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using different concentration of the components. The hydrogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and swelling degree; betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay shown that almost all hydrogels are cytocompatibles and an increase the proliferation in both cell types after one week of incubation was observed by Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics and biocompatibility.

Plant pathogenic fungi are the largest group of disease-causing agents on crop plants and represent a persistent and significant threat to agriculture worldwide. Conventional approaches based on the use of pesticides raise social concern for the impact on the environment and human health and alternative control methods are urgently needed. The rapid improvement and extensive implementation of RNAi technology for various model and non-model organisms has provided the initial framework to adapt this post-transcriptional gene silencing technology for the management of fungal pathogens. In this review, we describe exogenous RNAi involved in plant pathogenic fungi and discuss small RNA production, formulation, and RNAi delivery methods. We explore some challenges with possible solutions. Furthermore, exogenous RNAi holds great potential for RNAi-mediated plant pathogenic fungal disease control.

Statistical management policy and system plays significant role in development of any nation as it guides the planner to analyze the gaps, design programs and allocate budget in efficient manner. Globally, design and usage of statistical management system varies relying on country specific ability and resources availability. Government of Nepal has been managing database in individual as well as thematic manner. Policy wise, thematic database is in operation based on Statistics Act 1958 and individual database is in operation based on Birth, Death and Other Personal Related Events Registration Act 1976. Though civil registration related policies have been either updated or newly formed, sectoral statistic management related policy has not been updated since its first promulgation period (1958). With no policy supporting the consolidated statistical management system, government as well as non-government agencies has been investing millions of dollars annually to collect, compile and analyze individual related data and fulfill their respective objectives. It has forced the government services and performance to be paper-based, time-consuming and tedious thus creating dis-trust among citizen each passing day. Though, formulation of legal instrument promoted digital movement and mandated shift towards e-government modality, the process has been low. Theoretically, Technology Acceptance Model (TAM) state the need of having advanced and efficient technology to be in place in current setting to improve governance, efficiency, accountability, transparency and trust. Also, the same theory state the requirement of strong willingness and motivation from the users (government, non-government and citizen) to adopt the technology based policy and system. As the integrated statistical management policy emphasizes on technology-based system or digital system, the perspectives of Technology Acceptance Model also termed as Information System Theory aid in understanding the context, conceptualizing and addressing the needs with an establishment and implementation of digital system or technology based system. This policy paper applied the Technology Acceptance Model (TAP) to examine the underlying opportunities and challenges associated with an integrated statistical management policy. With existing gaps in existing policy, system and practice alongside an overview of opportunities and challenges, this paper recommends the need of stand-alone integrated statistical management policy to consolidate sectoral as well as civil related information through single system based on recommended policy.

The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells were its release from mitochondria and apoptosis induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and test their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA, and compared to a nanoparticle-free formulation. Overexpression of FA in LLC cells and internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) was confirmed by confocal microscopy. Caspase activation assays show NPs retain 88-96% Cyt c activity. The NP formulations were more efficient in decreasing LLC cell viability than the NP-free formulation, with IC50: 49.2 to 70.1 μg/ml versus 129.5 μg/ml, respectively. Our NP system is thrice as selective towards cancerous than normal cells. In-vivo studies using tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model.

Nanodiamonds of detonation origin are promising delivery agents of anti-cancer therapeutic compounds in a whole organism like mouse, owing to their versatile surface chemistry and ultra-small 5 nm average primary size compatible with natural elimination routes. However, to date, little is known about tissue distribution, elimination pathways and efficacy of nanodiamonds-based therapy in mice. In this report, we studied the capacity of cationic hydrogenated detonation nanodiamonds to carry active small interfering RNA (siRNA) in a mice model of Ewing sarcoma, a bone cancer of young adult due in the vast majority to the EWS-Fli1 junction oncogene. Replacing hydrogen gas by its radioactive analog tritium gas led to the formation of labeled nanodiamonds and allowed us to investigate their distribution throughout mouse organs and their excretion in urine and feces. We also demonstrated that siRNA directed against EWS-Fli1 inhibited this oncogene expression in tumor xenografted on mice. This work is a significant step to establish cationic hydrogenated detonation nanodiamond as an effective agent for in vivo delivery of active siRNA.

Amine containing polymers are extensively studied as special carriers for short-chain RNA (13–25 nucleotides) which are applied as gene silencing agent in gene therapy of various diseases including cancer. Elaboration of the oligonucleotide carriers requires knowledge about peculiarities of oligonucleotide - polymeric amine interaction. Critical length of the interacting chains is the important parameter which allows to design sophisticated constructions containing oligonucleotide binding segments, solubilizing, protective and aiming parts. We studied interaction of (TCAG)n, n=1-6 DNA oligonucleotides with polyethylenimine and poly(N-(3-((3-(dimethyl­amino)propyl)(methyl)amino)propyl)-N-methylacrylamide). Critical length for oligonucleotides in interaction with polymeric amines is 8-12 units and complexation at these length can be accompanied by "all-or-nothing" effects. New dimethylacrylamide based polymers with grafted polyamine chains were obtained and studied in complexation with DNA and RNA oligonucleotides. The most effective interaction and transfection activity into A549 cancer cells was found for a sample with average number of nitrogens in polyamine chain equal to 27, i.e. for a sample in which all grafted chains are longer the critical length for polymeric amine - oligonucleotide complexation.