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The rotor magnetic shunt structure hybrid excitation synchronous motor (RMS-HESM) has been widely used in marine propulsion due to its advantages of low loss and high efficiency. The objective of this paper is to improve the output torque capability of the hybrid excitation motor with a rotor magnetic shunt structure by conducting a multi-objective optimization design for the magnetic permeability structure. The first step involved establishing a mathematical analytical model of average torque and torque ripple based on the fundamental principle of motor magnetization. Next, the parameters of the magnetic permeability structure were designed and analyzed using the finite element simulation method. The impact of the variations in the parameters of the magnetic permeability structure on motor torque and no−load back electromotive force was examined. Additionally, a sensitivity analysis was performed on the design variables of the magnetic permeability structure, leading to the determination of optimization parameters based on the obtained results. The adaptive inertia weight-based particle swarm algorithm (PSO) was employed to conduct a multi-objective optimization design analysis. A comparative analysis on the average torque, torque ripple, and no−load back electromotive force of the motor before and after optimization was performed using the Maxwell and Workbench and Optislong joint simulation tools. This enhancement significantly improves the torque performance of the marine motor while simultaneously optimizing the no−load back electromotive force. [ABSTRACT FROM AUTHOR]

Gastric acid secretion is closely associated with the development and treatment of chronic gastritis, gastric ulcers, and reflux esophagitis. However, gastric acid secretion is affected by complex physiological and pathological factors, and real-time detection and control are complicated and expensive. A gastric delivery system for antacids and therapeutics in response to low pH in the stomach holds promise for smart and personalized treatment of stomach diseases. In this study, pH-responsive modular units were used to assemble various modular devices for self-regulation of pH and drug delivery to the stomach. The modular unit with a release window of 50 mm2 could respond to pH and self-regulate within 10 min, which is related to its downward floatation and internal gas production. The assembled devices could stably float downward in the medium and detach sequentially at specific times. The assembled devices loaded with antacids exhibited smart pH self-regulation under complex physiological and pathological conditions. In addition, the assembled devices loaded with antacids and acid suppressors could multi-pulse or prolong drug release after rapid neutralization of gastric acid. Compared with traditional coating technology, 3D printing can print the shell layer by layer, flexibly adjust the internal and external structure and composition, and assemble it into a multi-level drug release system. Compared with traditional coating, 3D-printed shells have the advantage of the flexible adjustment of internal and external structure and composition, and are easy to assemble into a complex drug delivery system. This provides a universal and flexible strategy for the personalized treatment of diseases with abnormal gastric acid secretion, especially for delivering acid-unstable drugs. [ABSTRACT FROM AUTHOR]

Mucosal drug delivery permits direct and prompt drug absorption, which is capable of reducing undesirable decomposition that occurs before absorption. However, mucus clearance of those mucosal drug delivery systems strongly retards their actual application. Herein, we propose chromatophore nanoparticles embedded with FOF1-ATPase motors to promote mucus penetration. The FOF1-ATPase motor-embedded chromatophores were firstly extracted from Thermus thermophilus by using a gradient centrifugation method. Then, the model drug (curcumin) was loaded onto the chromatophores. The drug loading efficiency and entrapment efficiency were optimized by using different loading approaches. The activity, motility, stability and mucus permeation of the drug-loaded chromatophore nanoparticles were thoroughly investigated. Both the in vitro and in vivo studies revealed that the FOF1-ATPase motor-embedded chromatophore successfully enhanced mucus penetration glioma therapy. This study indicates that the FOF1-ATPase motor-embedded chromatophore is a promising alternative as a mucosal drug delivery system. [ABSTRACT FROM AUTHOR]

As an oral mucosal drug delivery system, oral films have been of wide concern in recent years because of their advantages such as rapid absorption, being easy to swallow and avoiding the first-pass effect common for mucoadhesive oral films. However, the currently utilized manufacturing approaches including solvent casting have many limitations, such as solvent residue and difficulties in drying, and are not suitable for personalized customization. To solve these problems, the present study utilizes liquid crystal display (LCD), a photopolymerization-based 3D printing technique, to fabricate mucoadhesive films for oral mucosal drug delivery. The designed printing formulation includes PEGDA as the printing resin, TPO as the photoinitiator, tartrazine as the photoabsorber, PEG 300 as the additive and HPMC as the bioadhesive material. The influence of printing formulation and printing parameters on the printing formability of the oral films were elucidated in depth, and the results suggested that PEG 300 in the formulation not only provided the necessary flexibility of the printed oral films, but also improved drug release rate due to its role as pore former in the produced films. The presence of HPMC could greatly improve the adhesiveness of the 3D-printed oral films, but excessive HPMC increased the viscosity of the printing resin solution, which could strongly hinder the photo-crosslinking reaction and reduce printability. Based on the optimized printing formulation and printing parameters, the bilayer oral films containing a backing layer and an adhesive layer were successfully printed with stable dimensions, adequate mechanical properties, strong adhesion ability, desirable drug release and efficient in vivo therapeutic efficacy. All these results indicated that an LCD-based 3D printing technique is a promising alternative to precisely fabricate oral films for personalized medicine. [ABSTRACT FROM AUTHOR]

A key aspect of cytokine-induced changes as observed in sepsis is the dysregulated activation of endothelial cells (ECs), initiating a cascade of inflammatory signaling leading to leukocyte adhesion/migration and organ damage. The therapeutic targeting of ECs has been hampered by concerns regarding organ-specific EC heterogeneity and their response to inflammation. Using in vitro and in silico analysis, we present a comprehensive analysis of the proteomic changes in mouse lung, liver and kidney ECs following exposure to a clinically relevant cocktail of proinflammatory cytokines. Mouse lung, liver and kidney ECs were incubated with TNF-α/IL-1β/IFN-γ for 4 or 24 h to model the cytokine-induced changes. Quantitative label-free global proteomics and bioinformatic analysis performed on the ECs provide a molecular framework for the EC response to inflammatory stimuli over time and organ-specific differences. Gene Ontology and PANTHER analysis suggest why some organs are more susceptible to inflammation early on, and show that, as inflammation progresses, some protein expression patterns become more uniform while additional organ-specific proteins are expressed. These findings provide an in-depth understanding of the molecular changes involved in the EC response to inflammation and can support the development of drugs targeting ECs within different organs. Data are available via ProteomeXchange (identifier PXD031804). [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger–Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone. [ABSTRACT FROM AUTHOR]

In this study, a micro-molding technology was used to prepare the microneedles (MNs), while a texture analyzer was used to measure its Young's modulus, Poisson's ratio and compression breaking force, to evaluate whether the MNs can penetrate the skin. The effects of different materials were characterized by their ability to withstand stresses using the Structural Mechanics Module of COMSOL Multiphysics. Carboxymethylcellulose (CMC) was chosen as the needle formulation material with varying quantities of polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA) and hyaluronic acid (HA) to adjust the viscosity, brittleness, hardness and solubility of the material. The results of both the experimental tests and the predictions indicated that the hardest tip material had a solids content of 15% ( w / w ) with a 1:2 ( w / w ) CMC: HA ratio. Furthermore, it was shown that a solid content of 10% ( w / w ) with a 1:5 ( w / w ) CMC: PVA ratio is suitable for making patches. The correlation between the mechanical properties and the different materials was found using the simulation analysis as well as the force required for different dissolving microneedles (DMNs) to penetrate the skin, which significantly promoted the research progress of microneedle transdermal drug delivery. [ABSTRACT FROM AUTHOR]

The endothelium is the inner layer of all blood vessels and it regulates hemostasis. It also plays an active role in the regulation of the systemic inflammatory response. Systemic inflammatory disease often results in alterations in vascular endothelium barrier function, increased permeability, excessive leukocyte trafficking, and reactive oxygen species production, leading to organ damage. Therapeutics targeting endothelium inflammation are urgently needed, but strong concerns regarding the level of phenotypic heterogeneity of microvascular endothelial cells between different organs and species have been expressed. Microvascular endothelial cell heterogeneity in different organs and organ-specific variations in endothelial cell structure and function are regulated by intrinsic signals that are differentially expressed across organs and species; a result of this is that neutrophil recruitment to discrete organs may be regulated differently. In this review, we will discuss the morphological and functional variations in differently originated microvascular endothelia and discuss how these variances affect systemic function in response to inflammation. We will review emerging in vivo and in vitro models and techniques, including microphysiological devices, proteomics, and RNA sequencing used to study the cellular and molecular heterogeneity of endothelia from different organs. A better understanding of microvascular endothelial cell heterogeneity will provide a roadmap for developing novel therapeutics to target the endothelium. [ABSTRACT FROM AUTHOR]

Chitosan nanoparticles (CS-NPs) are under increasing investigation for the delivery of therapeutic proteins, such as vaccines, interferons, and biologics. A large number of studies have been taken on the characteristics of CS-NPs, and very few of these studies have focused on the microstructure of protein-loaded NPs. In this study, we prepared the CS-NPs by an ionic gelation method, and bovine serum albumin (BSA) was used as a model protein. Dynamic high pressure microfluidization (DHPM) was utilized to post-treat the nanoparticles so as to improve the uniformity, repeatability and controllability. The BSA-loaded NPs were then characterized for particle size, Zeta potential, morphology, encapsulation efficiency (EE), loading capacity (LC), and subsequent release kinetics. To improve the long-term stability of NPs, trehalose, glucose, sucrose, and mannitol were selected respectively to investigate the performance as a cryoprotectant. Furthermore, trehalose was used to obtain re-dispersible lyophilized NPs that can significantly reduce the dosage of cryoprotectants. Multiple spectroscopic techniques were used to characterize BSA-loaded NPs, in order to explain the release process of the NPs in vitro. The experimental results indicated that CS and Tripolyphosphate pentasodium (TPP) spontaneously formed the basic skeleton of the NPs through electrostatic interactions. BSA was incorporated in the basic skeleton, adsorbed on the surface of the NPs (some of which were inlaid on the NPs), without any change in structure and function. The release profiles of the NPs showed high consistency with the multispectral results. [ABSTRACT FROM AUTHOR]

In this paper, an all-solid-state nitrate doped polypyrrole (PPy(NO3−) ion-selective electrode (ISE) was prepared with a nanohybrid composite film of gold nanoparticles (AuNPs) and electrochemically reduced graphene oxide (ERGO). Preliminary tests on the ISE based in-situ soil nitrate–nitrogen (NO3−-N) monitoring was conducted in a laboratory 3-stage column. Comparisons were made between the NO3−-N content of in-situ soil percolate solution and laboratory-prepared extract solution. Possible influential factors of sample depth, NO3−-N content, soil texture, and moisture were varied. Field-emission scanning electron microscopy (FESEM) and X-ray powder diffraction (XRD) characterized morphology and content information of the composite film of ERGO/AuNPs. Due to the performance excellence for conductivity, stability, and hydrophobicity, the ISE with ERGO/AuNPs illustrates an acceptable detection range from 10−1 to 10−5 M. The response time was determined to be about 10 s. The lifetime was 65 days, which revealed great potential for the implementation of the ERGO/AuNPs mediated ISE for in-situ NO3−-N monitoring. In-situ NO3−-N testing results conducted by the all-solid-state ISE followed a similar trend with the standard UV-VIS method. [ABSTRACT FROM AUTHOR]

The high printing efficiency and easy availability of desktop digital light processing (DLP) printers have made DLP 3D printing a promising technique with increasingly broad application prospects, particularly in personalized medicine. The objective of this study was to fabricate and evaluate medical samples with external and internal structures using the DLP technique. The influence of different additives and printing parameters on the printability and functionality of this technique was thoroughly evaluated. It was observed that the printability and mechanical properties of external structures were affected by the poly(ethylene glycol) diacrylate (PEGDA) concentration, plasticizers, layer height, and exposure time. The optimal printing solutions for 3D external and internal structures were 100% PEGDA and 75% PEGDA with 0.25 mg/mL tartrazine, respectively. And the optimal layer height for 3D external and internal structures were 0.02 mm and 0.05 mm, respectively. The optimal sample with external structures had an adequate drug-loading ability, acceptable sustained-release characteristics, and satisfactory biomechanical properties. In contrast, the printability of internal structures was affected by the photoabsorber, PEGDA concentration, layer height, and exposure time. The optimal samples with internal structures had good morphology, integrity and perfusion behavior. The present study showed that the DLP printing technique was capable of fabricating implants for drug delivery and physiological channels for in vivo evaluation. [ABSTRACT FROM AUTHOR]

In this work, ammonium pyrrolidine dithiocarbamate (APDC) was used as a surface etchant to modify CdTe/CdS core-shell quantum dots (QDs). The APDC etchant combines with the cadmium ions (Cd2+) on the surface of the QDs, resulting in the formation of surface holes. The formation of these holes changes the QD surface structure, which leads to fluorescence quenching of the QDs. Newly added Cd2+ can selectively recognize and combine with these holes; thus, the fluorescence intensity of the QDs can be restored. The linear response of this turn-on fluorescent sensor was found to be 0–100 μg/L and 100–600 μg/L under the determined optimal conditions, and its limit of detection (LOD) for Cd2+ was 2.642 μg/L (23.5 nmol/L). [ABSTRACT FROM AUTHOR]

Soil nitrate–nitrogen (NO3−-N) is one of the primary factors used to control nitrogen topdressing application during the crop growth period. The ion-selective electrode (ISE) is a promising method for rapid lower-cost in-field detection. Due to the simplification of sample preparation, the accuracy and stability of ISE-based in-field detection is doubted. In this paper, a self-designed prototype system for on-site soil NO3−-N detection was developed. The procedure of spinning centrifugation was used to avoid interference from soil slurry suspension. A modified Nernstian prediction model was quantitatively characterized with outputs from both the ISE and the soil moisture sensor. The measurement accuracy of the sensor fusion model was comparable with the laboratory ISE detections with standard sample pretreatment. Compared with the standard spectrometric method, the average absolute error (AE) and root-mean-square error (RMSE) were found to be less than 4.7 and 6.1 mg/L, respectively. The on-site soil testing efficiency was 4–5 min/sample, which reduced the operation time by 60% compared with manual sample preparation. The on-site soil NO3−-N status was dynamically monitored for 42 consecutive days. The declining peak of NO3−-N was observed. In all, the designed ISE-based detection system demonstrated a promising capability for the dynamic on-site monitoring of soil macronutrients. [ABSTRACT FROM AUTHOR]

Drug hydrolytic degradation, caused by atmospheric and inherent humidity, significantly reduces the therapeutic effect of pharmaceutical solid dosages. Moisture barrier film coating is one of the most appropriate and effective approaches to protect the active pharmaceutical ingredients (API) from hydrolytic degradation during the manufacturing process and storage. Coating formulation design and process control are the two most commonly used strategies to reduce water vapor permeability to achieve the moisture barrier function. The principles of formulation development include designing a coating formulation with non-hygroscopic/low water activity excipients, and formulating the film-forming polymers with the least amount of inherent moisture. The coating process involves spraying organic or aqueous coating solutions made of natural or synthetic polymers onto the surface of the dosage cores in a drum or a fluid bed coater. However, the aqueous coating process needs to be carefully controlled to prevent hydrolytic degradation of the drug due to the presence of water during the coating process. Recently, different strategies have been designed and developed to effectively decrease water vapor permeability and improve the moisture barrier function of the film. Those strategies include newly designed coating formulations containing polymers with optimized functionality of moisture barrier, and newly developed dry coating processes that eliminate the usage of organic solvent and water, and could potentially replace the current solvent and aqueous coatings. This review aims to summarize the recent advances and updates in moisture barrier coatings. [ABSTRACT FROM AUTHOR]

Protein Kinase C (PKC) is a family composed of phospholipid-dependent serine/threonine kinases that are master regulators of inflammatory signaling. The activity of different PKCs is context-sensitive and these kinases can be positive or negative regulators of signaling pathways. The delta isoform (PKCδ) is a critical regulator of the inflammatory response in cancer, diabetes, ischemic heart disease, and neurodegenerative diseases. Recent studies implicate PKCδ as an important regulator of the inflammatory response in sepsis. PKCδ, unlike other members of the PKC family, is unique in its regulation by tyrosine phosphorylation, activation mechanisms, and multiple subcellular targets. Inhibition of PKCδ may offer a unique therapeutic approach in sepsis by targeting neutrophil-endothelial cell interactions. In this review, we will describe the overall structure and function of PKCs, with a focus on the specific phosphorylation sites of PKCδ that determine its critical role in cell signaling in inflammatory diseases such as sepsis. Current genetic and pharmacological tools, as well as in vivo models, that are used to examine the role of PKCδ in inflammation and sepsis are presented and the current state of emerging tools such as microfluidic assays in these studies is described. [ABSTRACT FROM AUTHOR]