Modulated Radio Frequency Stealth Waveforms for Ultra-Wideband Radio Fuzes.

The increasingly complex electromagnetic environment of modern warfare and the proliferation of intelligent jamming threaten to reduce the survival rate of radio fuzes on the battlefield. Radio frequency (RF) stealth technology can fundamentally improve the anti-interception and reconnaissance capabilities of radio fuzes, thereby lessening the probability of them being intercepted, recognized, and jammed by the enemy. In this paper, an RF stealth waveform based on chaotic pulse-position modulation is proposed for ultra-wideband (UWB) radio fuzes. Adding a perturbation signal based on the Tent map ensures that the chaotic sequences have sufficiently long periods despite hardware byte limitations. Measuring the approximate entropy and sequence period shows that the Tent map with the addition of perturbation signals can maintain good randomness under byte constraints, closely approximating the Tent map with ideal precision. Simulations verify that the proposed chaotic mapping used to modulate the pulse position of an ultra-wideband radio fuze signal results in superior detection, anti-interception, and anti-jamming performance.

Primaquine Loaded Solid Lipid Nanoparticles (SLN), Nanostructured Lipid Carriers (NLC), and Nanoemulsion (NE): Effect of Lipid Matrix and Surfactant on Drug Entrapment, in vitro Release, and ex vivo Hemolysis.

Primaquine (PQ), an 8-aminoquinoline antimalarial drug, has been widely used for the eradication of hypnozoites from the liver and, therefore, recognized as the radical cure of malaria. However, the clinical applications of PQ are restricted to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency due to severe dose-related hemolytic side effects. Nanoparticle carriers have shown great potential in achieving higher PQ concentrations in the target site, thereby reducing dose-related systemic toxicity caused by non-specific exposure. This work aims to develop, compare, and evaluate three PQ-loaded lipid-based drug carriers including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nano-emulsions (NE). The optimized PQ-SLN, PQ-NLC, and PQ-NE had a particle size of 250 nm, a PDI range of 0.1 to 0.3, a zeta potential of - 30 mV, and entrapment efficiency of ~ 90%. All lipid formulations showed sustained release in both simulated gastric and intestinal fluids over 6 h. Four empirical models - including zero-order, Higuchi, Korsmeyer-Peppas, and Hixson-Crowell models - were tested to understand the drug release mechanisms of PQ-SLN, PQ-NLC, and PQ-NE. The model fitness was found to be the highest in the Korsmeyer-Peppas model for all the PQ-loaded lipid formulations (R2: 0.88-0.94). No significant changes were observed in the entrapment efficiency, particle size, and PDI of lipid formulations throughout 1 month of storage at 4 °C and 25 °C. PQ-SLN and PQ-NLC can be further lyophilized with cryoprotectants to improve long-term stability. Finally, the treatment of erythrocytes with PQ-SLN, PQ-NLC, and PQ-NE reduced erythrocyte hemolysis by approximately 4.5-fold compared to the free drug solution.

Microbial Stability of Pharmaceutical and Cosmetic Products.

This review gives a brief overview about microbial contamination in pharmaceutical products. We discuss the distribution and potential sources of microorganisms in different areas, ranging from manufacturing sites, pharmacy stores, hospitals, to the post-market phase. We also discuss the factors that affect microbial contamination in popular dosage forms (e.g., tablets, sterile products, cosmetics). When these products are contaminated, the microorganisms can cause changes. The effects range from mild changes (e.g., discoloration, texture alteration) to severe effects (e.g., changes in activities, toxicity). The most common method for countering microbial contamination is the use of preservatives. We review some frequently used preservatives, and we describe the mechanisms by which microorganisms develop resistance to these preservatives. Finally, because preservatives are inherently toxic, we review the efforts of researchers to utilize water activity and other non-preservative approaches to combat microbial contamination.

Understanding syringeability and injectability of high molecular weight PEO solution through time-dependent force-distance profiles.

Opioid medications play a vital role in treating moderate to severe pain. Unfortunately, many drug misusers and abusers attempt to alter the formulations or properties of these drugs by manipulation, (e.g., crushing, chewing, smoking, snorting, injecting). The intravenous (IV) route is most dangerous to abusers, as the drugs directly enter the circulatory system and produce intense euphoria. To obtain a full understanding of the impact of syringe factors (e.g., needle gauge size, needle length, syringe barrel size), on the ease of injection, we undertook a comprehensive assessment of syringeability and injectability of manipulated abuse-deterrent formulations (ADFs). A texture analyzer-based testing method was developed for the measurement of the resistance force of pulling, holding, and pushing phases of injections. Results showed that the finer needle gauge sizes required higher injection force to withdraw drug solutions. In addition, the syringed liquid volume was highly dependent on needle gauge size, holding time, and sample viscosity. In most cases, a lower needle gauge number and a longer holding time increased the syringed volume. Needle length was highly correlated to injection force (R2 = 0.99). Using longer needles to inject drug solution requires greater force. Furthermore, large barrel size was correlated to pushing force (R2 = 0.99); thus, increasing the difficulty of pushing the plunger of a large syringe with one hand. Finally, relationships between injection force, sample viscosity, and testing conditions were elucidated using a mathematical model, which could be used in the future to assess and predict injection force of solution samples.

Continuous monitoring of a monoclonal antibody by size exclusion chromatography reveals a correlation between system suitability parameters and column aging.

Size exclusion chromatography (SEC) is a foundational analytical method to assess product purity of biological molecules. To ensure accurate and reproducible data that meet regulatory agency standards, it is critical to monitor the chromatographic column with efficient and continuous approaches. In this study, 19 SEC columns (Waters Acquity BEH200) were evaluated using an in-house monoclonal antibody made at Regeneron. System suitability parameters (SSPs) were used to monitor the performance of the SEC assay, including USP resolution, USP plate count, USP tailing factor, asymmetry factor, elution time, peak width, and peak height. A general linear model was built and revealed that elution time, peak width, asymmetry factor, and tailing factor increased with injection number, while peak height, resolution, and plate count decreased. After 1000 injections, tailing factor and peak width increased by more than 10%, while resolution and plate count decreased by more than 10% from their respective starting values.

The effect of food vehicles on in vitro performance of pantoprazole sodium delayed release sprinkle formulation.

Certain patient populations, including children, the elderly or people with dysphagia, find swallowing whole medications such as tablets and capsules difficult. To facilitate oral administration of drugs in such patients, a common practice is to sprinkle the drug products (e.g., usually after crushing the tablet or opening the capsule) on food vehicles before consumption which improves swallowability. Thus, evaluation of the impact of food vehicles on the potency and stability of the administered drug product is important. The aim of the current study was to evaluate the physicochemical properties (viscosity, pH, and water content) of common food vehicles used for sprinkle administration (e.g., apple juice, applesauce, pudding, yogurt, and milk) and their impacts on the in vitro performance (i.e., dissolution) of pantoprazole sodium delayed release (DR) drug products. The food vehicles evaluated exhibited marked difference in viscosity, pH and water content. Notably, the pH of the food as well as the interaction between food vehicle pH and drug-food contact time were the most significant factors affecting the in vitro performance of pantoprazole sodium DR granules. For example, the dissolution of pantoprazole sodium DR granules sprinkled on food vehicles of low pH (e.g., apple juice or applesauce) for short durations remained unchanged compared with the control group (i.e., without mixing with food vehicles). However, use of high pH food vehicles (e.g., milk) with prolonged contact time (e.g., 2 h) resulted in accelerated pantoprazole release, drug degradation and loss of potency. Overall, a thorough assessment of physicochemical properties of food vehicles and formulation characteristics are a necessary part of the development of sprinkle formulations.

Carbon-incorporated bimetallic phosphide nanospheres derived from MOFs as superior electrocatalysts for hydrogen evolution.

Preparing low-cost and highly efficient electrocatalysts for the hydrogen evolution reaction using a simple strategy still faces challenges. In this work, we proposed a facile phosphating process to successfully transform CoFe-BTC (BTC = 1,3,5-benzenetricarboxylate) precursors into carbon-incorporated bimetallic phosphide (CoFe-P/C) nanospheres. Due to the synergistic effect between bimetals and uniformly covered carbon shells outside, the as-synthesized porous bimetallic phosphide nanospheres exhibit superior HER activity, enhanced kinetics, and excellent cycle durability in both acidic and alkaline solutions. The optimized material could afford a current density of 10 mA cm-2 with overpotentials of 138 and 193 mV for the HER in acidic and alkaline solutions, respectively. Meanwhile, it delivered small Tafel slopes of 84 and 78 mV dec-1 for the HER in 0.5 M H2SO4 and 1.0 M KOH, respectively. Moreover, an assembled alkaline electrolyzer enabled a low voltage of 1.62 V to drive a current density of 10 mA cm-2 for overall water splitting. DFT calculations indicate that the CoP-Fe2P composite is supposed to exhibit better HER performance than each component, revealing the vital role of the interfacial site in catalyzing the HER.

Vibration Control of Time-Varying Delay under Complex Excitation.

The existing available research outcomes on vibration attenuation control for time-delay feedback indicate that, for the delay dynamic vibration absorber with fixed time-delay control parameters, under harmonic excitation, a good vibration attenuation control effect occurs on the vibration of the main system. However, the effect is not obvious for complex excitation. Aiming at the above problems, in a short time interval, a harmonic excitation with the same displacement size as the complex excitation was established. Then, by calculating its equivalent amplitude and equivalent frequency, a harmonic equivalent method for complex excitation was proposed in this paper. The time-delay parameters were adjusted according to the equivalent frequency of harmonic equivalent excitation in real time; therefore, a good vibration attenuation control effect was obtained through the delay dynamic vibration absorber in the discrete time interval. In this paper, research on a time-varying delay dynamic vibration absorber was conducted by taking the two-degree-of-freedom vibration system with a delay dynamic vibration absorber as an example. The simulation results show that the proposed control method can reduce the vibration of the main system by about 30% compared with the passive vibration absorber. This can obviously improve the performance of the time-delay dynamic vibration absorber. It provides a new technical idea for the design of vehicle active frame system.

CIRD-F: Spread and Influence of COVID-19 in China.

The outbreak of coronavirus disease 2019 (COVID-19) has been spreading rapidly in China and the Chinese government took a series of policies to control the epidemic. Therefore, it will be helpful to predict the tendency of the epidemic and analyze the influence of official policies. Existing models for prediction, such as cabin models and individual-based models, are either oversimplified or too meticulous, and the influence of the epidemic was studied much more than that of official policies. To predict the epidemic tendency, we consider four groups of people, and establish a propagation dynamics model. We also create a negative feedback to quantify the public vigilance to the epidemic. We evaluate the tendency of epidemic in Hubei and China except Hubei separately to predict the situation of the whole country. Experiments show that the epidemic will terminate around 17 March 2020 and the final number of cumulative infections will be about 78 191 (prediction interval, 74 872 to 82 474). By changing the parameters of the model accordingly, we demonstrate the control effect of the policies of the government on the epidemic situation, which can reduce about 68% possible infections. At the same time, we use the capital asset pricing model with dummy variable to evaluate the effects of the epidemic and official policies on the revenue of multiple industries.

Optimization, stabilization, and characterization of amphotericin B loaded nanostructured lipid carriers for ocular drug delivery.

The current study sought to formulate, optimize, and stabilize amphotericin B (AmB) loaded PEGylated nanostructured lipid carriers (NLC) and to study its ocular biodistribution following topical instillation. AmB loaded PEGylated NLC (AmB-PEG-NLC) were fabricated by hot-melt emulsification followed by high-pressure homogenization (HPH) technique. 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-2K-DSPE) was used for surface PEGylation. mPEG-DSPE with different PEG molecular weight, 1 K, 2 K, 5 K, 10 K, and 20 K, were screened for formulation stability. Furthermore, the AmB loaded PEGylated (2K) NLC (AmB-PEG2K-NLC) was optimized using Box-Behnken design with respect to the amount of AmB, castor oil, mPEG-2K-DSPE, and number of high-pressure homogenization cycles as the factors; particle size, zeta potential, PDI, entrapment efficiency, and loading efficiency as responses. Stability of the optimized AmB-PEG2K-NLC was assessed over 4 weeks, at 4 °C as well as 25 °C and effect of autoclaving was also evaluated. AmB-PEG2K-NLC were tested for their in vitro antifungal activity against Candida albicans (ATCC 90028), AmB resistant Candida albicans (ATCC 200955) and Aspergillus fumigatus (ATCC 204305). Cytotoxicity of AmB-PEG2K-NLC was studied in human retinal pigmented epithelium cells. In vivo ocular biodistribution of AmB was evaluated in rabbits, following topical application of PEGylated NLCs or marketed AmB preparations. PEGylation with mPEG-2K-DSPE prevented leaching of AmB and increased the drug load significantly. The optimized formulation was prepared with a particle size of 218 ±â€¯5 nm; 0.3 ±â€¯0.02 PDI, 4.6 ±â€¯0.1% w/w drug loading, and 92.7 ±â€¯2.5% w/w entrapment efficiency. The optimized colloidal dispersions were stable for over a month, at both 4 °C and 25 °C. AmB-PEG2K-NLCs showed significantly (p < 0.05) better antifungal activity in both wild-type and AmB resistant Candida strains and, was comparable to, or better than, commercially available parenteral AmB formulations like Fungizone™ and AmBisome®. AmB-PEG2K-NLC did not show any toxicity up to a highest concentration of 1% (v/v) (percent formulation in medium). Following topical instillation, AmB was detected in all the ocular tissues tested and statistically significant (p > 0.05) difference was not observed between the formulations tested. An optimized autoclavable and effective AmB-PEG2K-NLC ophthalmic formulation with at least one-month stability, in the reconstituted state, has been developed.

Decellularized cartilage as a prospective scaffold for cartilage repair.

Articular cartilage lacks self-healing capacity, and there is no effective therapy facilitating cartilage repair. Osteoarthritis (OA) due to cartilage defects represents large and increasing healthcare burdens worldwide. Nowadays, the generation of scaffolds to preserve bioactive factors and the biophysical environment has received increasing attention. Furthermore, improved decellularization technology has provided novel insights into OA treatment. This review provides a comparative account of different cartilage defect therapies. Furthermore, some recent effective decellularization protocols have been discussed. In particular, this review focuses on the decellularization ratio of each protocol. Moreover, these protocols were compared particularly on the basis of immunogenicity and mechanical functionality. Further, various recellularization methods have been enlisted and the reparative capacity of decellularized cartilage scaffolds is evaluated herein. The advantages and limitations of different recellularization processes have been described herein. This provides a basis for the generation of decellularized cartilage scaffolds, thereby potentially promoting the possibility of decellularization as a clinical therapeutic target.

Primary chondrocyte exosomes mediate osteoarthritis progression by regulating mitochondrion and immune reactivity.

Aim: We aimed to investigate the proteomics of primary chondrocyte exosomes and the effect of exosomes in osteoarthritis (OA) treatment. Materials & methods: We isolated exosomes from primary chondrocytes cultured in normal (D0) and inflammatory environments induced by IL-1ß and determined the proteomics of these exosomes. Next, we investigated what effect and mechanism D0 chondrocytes exosomes have in OA treatment. Results: There were more proteins that belonged to mitochondrion and were involved in immune system processes in D0 exosomes. Notably, intra-articular administration of D0 exosomes successfully prevented the development of OA. D0 chondrocyte exosomes could restore mitochondrial dysfunction and polarize macrophage response toward an M2 phenotype. Conclusion: Our findings demonstrated that primary chondrocyte exosomes are efficient in OA treatment.

Formulation Development, Optimization, and In Vitro-In Vivo Characterization of Natamycin-Loaded PEGylated Nano-Lipid Carriers for Ocular Applications.

The present study aimed at formulating and optimizing natamycin (NT)-loaded polyethylene glycosylated nano-lipid carriers (NT-PEG-NLCs) using Box-Behnken design and investigating their potential in ocular applications. Response surface methodology computations and plots for optimization were performed using Design-Expert® software to obtain optimum values for response variables based on the criteria of desirability. Optimized NT-PEG-NLCs had predicted values for the dependent variables which are not significantly different from the experimental values. NT-PEG-NLCs were characterized for their physicochemical parameters; NT's rate of permeation and flux across rabbit cornea was evaluated, in vitro, and ocular tissue distribution was assessed in rabbits, in vivo. NT-PEG-NLCs were found to have optimum particle size (<300 nm), narrow polydispersity index, and high NT entrapment and NT content. In vitro transcorneal permeability and flux of NT from NT-PEG-NLCs was significantly higher than that of Natacyn®. NT-PEG-NLC (0.3%) showed improved delivery of NT across the intact cornea and provided concentrations statistically similar to the marketed suspension (5%) in inner ocular tissues, in vivo, indicating that it could be a potential alternative to the conventional suspension during the course of fungal keratitis therapy.

Biodiesel production from waste chicken fat with low free fatty acids by an integrated catalytic process of composite membrane and sodium methoxide.

An integrated process of catalytic composite membranes (CCMs) and sodium methoxide was developed to produce biodiesel from waste chicken fat. The free fatty acids (FFAs) in the chicken oil were converted to methyl esters by esterification with methanol using a novel sulfonated polyethersulfone (SPES)/PES/non-woven fabric (NWF) CCMs in a flow-through catalytic membrane reactor. The CCM is that the NWF fibers were fully embedded in SPES/PES with a homogeneous and microporous structure. The oil obtained after esterification was carried out by transesterification of sodium methoxide. The results showed that the FFAs conversion obtained by CCMs with the acid capacity of 25.28 mmol (H(+)) was 92.8% at the residence time 258s. The CCMs present a good stability during the continuous running of 500 h. The conversion of transesterification was 98.1% under the optimum conditions. The quality of the biodiesel met the international standards.

Death receptor 5-mediated TNFR family signaling pathways modulate γ-humulene-induced apoptosis in human colorectal cancer HT29 cells.

A component from Emilia sonchifolia (L.) DC, γ-humulene, was investigated. Significantly decreased cell viability of human colorectal cancer HT29 cells in a dose-dependent manner with IC50 53.67±2.99 µM for 24-h treatment was found. γ-Humulene induced apoptotic cell death and apoptosis was confirmed by morphological assessment. The staining with propidium iodide (PI) and flow cytometric analysis also showed that γ-humulene significantly promoted the sub-G1 phase (an apoptotic population) in HT29 cells. Colorimetric assays indicated that pretreatment with a specific inhibitor of caspase-8 (Z-IETD-FMK) significantly reduced activities of caspase-8 and caspase-3 in examined HT29 cells. γ-Humulene stimulated the death receptor 5 (DR5), DR4, Fas-associated protein with death domain (FADD), the cleavage of caspase-8 and cleavage caspase-3, but reduced the protein levels of cellular Fas-associated death-domain-like IL-1ß-converting enzyme inhibitory protein (c-FLIP) by Western blot analysis. Consequently, γ-humulene-triggered cell death was significantly attenuated by DR5 siRNA and the caspase-8 inhibitor. Based on our results, we suggest that γ-humulene induced apoptotic cell death in HT29 cells through a DR5-mediated caspase-8 and -3-dependent signaling pathway. Therefore, this agent might be useful for developing new therapeutic regimens for treatment of colorectal cancer in the future.