Inhaled heparin: Past, present, and future.

While heparin has traditionally served as a key anticoagulant in clinical practice for nearly a century, recent years have witnessed a growing interest in its role as a potent antiinflammatory and antiviral agent, as well as an anticancer agent. To address challenges with injection-based delivery, exploring patient-friendly routes such as oral and pulmonary delivery is crucial. This review specifically highlights the multiple therapeutic benefits of inhaled heparin. In summary, this review serves as a valuable source of information, providing deep insights into the diverse therapeutic advantages of inhaled heparin and its potential applications within clinical contexts.

Gut microbiota-derived gamma-aminobutyric acid from metformin treatment reduces hepatic ischemia/reperfusion injury through inhibiting ferroptosis.

Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was confirmed by the results of fecal microbiota transplantation treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase and putrescine aminotransferase, in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite.

Effects of Lipids and Type of Amino Acid in Protein in Microalgae on Nitrogen Reaction Pathways during Hydrothermal Liquefaction.

It is meaningful to understand the conversion pathways of nitrogen during the hydrothermal liquefaction process of microalgae to reveal the related reaction mechanisms and develop effective methods to prevent N from ending in biocrude, which eventually increases the quality of biocrude. Extending from our previous works that mainly focused on two high-protein (>50 wt%) microalgae (Chlorella sp. and Spirulina sp.), Nannochloropsis sp., which has a high lipid content (>70 wt%), was used as the feedstock for this project using the same methodology. The high lipid content in Na. induced less nitrogen during the oil phase and as a result, reduced the heteroatom content while also improving the quality of biocrude. It is worth noting that another investigation was conducted on the model compounds with different types of amino acids to specify the effects of the types of amino acids in the proteins in microalgae on the N pathway and their distribution in the products (aqueous phase, oil, solid, and gas). It was found that the basic amino acid in microalgae caused the formation of more N-heterocyclic compounds in the biocrude. The mass flow based on the mass balance was demonstrated to further refine the map showing the predicted reaction pathway of nitrogen from the previous version.

Investigation on the influence of design features on the performance of dry powder inhalers: Spiral channel, mouthpiece dimension, and gas inlet.

As inhaler design is rarely studied but critically important in pulmonary drug delivery, this study investigated the influence of inhaler designs, including a novel spiral channel, mouthpiece dimensions (diameter and length) as well as gas inlet. Experimental dispersion of a carrier-based formulation in conjugation with computational fluid dynamics (CFD) analysis, was performed to determine how the designs affect inhaler performance. Results reveal that inhalers with a narrow spiral channel could effectively increase drug-carrier detachment by introducing high velocity and strong turbulent flow in the mouthpiece, although the drug retention in the device is significantly high. It is also found that reducing mouthpiece diameter and gas inlet size could greatly improve the fine particle dose delivered to the lungs, whereas the mouthpiece length plays a trivial influence on the aerosolization performance. This study contributes toward a better understanding of inhaler designs as relevant to overall inhaler performance, and sheds light on how the designs affect device performance.

The effects of grid design on the performance of 3D-printed dry powder inhalers.

The grid structure is an indispensable part of most dry powder inhalers, but the effects of grid geometry on inhaler performance are rarely reported. This study aims to systemically investigate the influence of grid design on the aerosolization performance of capsule-based inhalers through experiments and computational analysis. In-vitro aerosolization and deposition performance of commercial and 3D-printed customized inhalers with different grid mesh designs were experimentally studied using a Next Generation Impactor (NGI). Flow fields in the inhalers were generated, and average turbulence kinetic energy (TKE) and airstream trajectories were obtained through Computational Fluid Dynamics (CFD) analysis, delineating the effects of the different grid designs. Comparative studies using the commercial inhalers and the 3D-printed inhalers show a slightly better performance for the latter, probably due to the different materials used for the inhalers, confirming the suitability of 3D printing. Experimental results show that intensive grid meshes with a relatively small aperture size are beneficial to enhancing inhaler performance. Computational results illustrate that the intensive grid meshes can reduce vortexed airstreams and increase turbulent kinetic energy at the grids in general, which also supports the experimental results. In summary, inhalers with intensive grid meshes are preferred for capsule-based inhalers to enhance aerosolization performance. These findings have significant implications for the comprehensive understanding of how grid designs influence inhaler performance.

The future of dry powder inhaled therapy: Promising or discouraging for systemic disorders?

Dry powder inhalation therapy has been shown to be an effective method for treating respiratory diseases like asthma, Chronic Obstructive Pulmonary Diseases and Cystic Fibrosis. It has also been widely accepted and used in clinical practices. Such success has led to great interest in inhaled therapy on treating systemic diseases in the past two decades. The current coronavirus (COVID-19) pandemic also has increased such interest and is triggering more potential applications of dry powder inhalation therapy in vaccines and antivirus drugs. Would the inhaled dry powder therapy on systemic disorders be as encouraging as expected? This paper reviews the marketed and in-development dry powder inhaler (DPI) products on the treatment of systemic diseases, their status in clinical trials, as well as the potential for COVID-19 treatment. The advancements and unmet problems on DPI systems are also summarized. With countless attempts behind and more challenges ahead, it is believed that the dry powder inhaled therapy for the treatment of systemic disorders still holds great potential and promise.

Comparison of carrier particles in the gas-liquid-solid inverse fluidised bed bioreactor.

The performance and energy consumption of a gas-liquid-solid inverse fluidised bed bioreactor (GLS-IFBBR) using polyethylene (PE) particles with different surface coatings (zeolite, lava rock, activated carbon and multi-plastic) as media for synthetic wastewater treatment were investigated at loading rates of 1.64-3.38 kg COD/(m3·d) and 0.17-0.34 kg N/(m3·d) to determine the optimum carrier media. The results showed that PE coated with other inorganic materials could increase the nutrient removal efficiency at the same influent conditions. Compared with other media, PE coated with zeolite (PEZ) was the optimal carrier particles in this study as reflected by the highest COD and nitrogen removal, stable effluent, low biomass yield at different hydraulic retention times (HRT). In addition, the energy consumption of lavarock-coated PE (PEL) with a highest density was the lowest.

The circulating fluidized bed bioreactor as a biological nutrient removal process for municipal wastewater treatment: Process modelling and costing analysis.

Emerging technologies for wastewater treatment face an uphill battle to be adopted in practice because no large-scale costing data exists to prove their cost competitiveness. Similar technologies and their costing data offer some insight to the approximate cost, but more detailed estimates are required for a final decision on process selection. The circulating fluidized bed bioreactor (CFBBR) is one such technology, proven at the lab and pilot and scale, but is yet to be used on a large scale. In order to demonstrate the potential economic competitiveness of the CFBBR, a method of modifying the CapdetWorks costing software by first modeling the CFBBR in the GPS-X process simulation software was employed. The modelling was used to determine the necessary changes to a moving bed bioreactor (MBBR) process (media size, density, surface area, and bed fill fraction) in CapdetWorks to simulate the CFBBR and then generate costing estimates for both capital cost (CapEx) and operation and maintenance cost (OpEx). Benchmarking the cost estimates against simulations of conventional suspended and attached growth processes and external costing data from the US EPA was performed to both validate the costing method and analyze the CFBBR's economic competitiveness. The calculation of the net present value from the CapEx and OpEx showed that the CFBBR is predicted to have 10%-30% lower costs at low flows of 1.5 and 4.6 MGD and comparative costs to conventional processes at higher flows from 10 to 30 MGD. Furthermore, the smaller land footprint of the CFBBR-based plants and lower landfilled biosolids implies that the CFBBR's environmental footprint is superior to its competitors and offers advantages for both small-sized plants and large urban plants.

Solvent-Free Fabrication of Robust Superhydrophobic Powder Coatings.

Superhydrophobicity originating from the "lotus effect" enables novel applications such as self-cleaning, anti-fouling, anti-icing, anti-corrosion, and oil-water separation. However, their real-world applications are hindered by some main shortcomings, especially the organic solvent problem, complex chemical modification of nanoparticles, and poor mechanical stability of obtained surfaces. Here, we report for the first time the solvent-free, chemical modification-free, and mechanically, chemically, and UV robust superhydrophobic powder coatings. The coatings were fabricated by adding commercially available polytetrafluoroethylene (PTFE) particles into powder coatings and by following the regular powder-coating processing route. The formation of such superhydrophobic surfaces was attributed to PTFE particles, which hindered the microscale leveling of powder coatings during curing. Through adjusting the dosage of PTFE, the hydrophobicity of obtained coatings can be tuned in a large range (water contact angle from 92 to 162°). The superhydrophobic coatings exhibited remarkable mechanical robustness against abrasion because of the unique hierarchical micro/nanoscale roughness and low surface energy throughout the coating and the solid lubrication effect of PTFE particles. The coatings also have robustness against chemical corrosion and UV irradiation owing to high bonding energy and chemical inertness of PTFE. Moreover, the coatings show attractive performances including self-cleaning, anti-rain, anti-snow, and anti-icing. With these multifaceted features, such superhydrophobic coatings are promising for outdoor applications. This study also contributes to the preparation of robust superhydrophobic surfaces in an environmentally friendly way.

Development of a novel silver ions-nanosilver complementary composite as antimicrobial additive for powder coating.

Applying silver into coatings has become a prevalent method in fabricating antimicrobial surfaces. However, the concerns about durability always exist and limit its applications. Here, a highly inhibitory, active, durable, and easy-to-use silver ions-nanosilver antimicrobial additive for powder coatings was fabricated in this study. Silver nanoparticles were chemically bonded to the Ag, Cu, and Zn-ternary ion-exchanged zeolite by α -lipoic acid, which was then encapsulated by hydrophilic polymers. The fabricated silver ions and silver nanoparticles (Ag+-AgNPs) complementary structure provides a synergistic effect. Ag+ is the main antimicrobial agent, while AgNPs act as a supplementary reservoir of Ag+. As well, the formed thin layer of silver nanoparticles and hydrophilic film prolongs the release of active Ag+ from zeolite, and Ag+ facilitates the activation of AgNPs. The results show that this additive indicates excellent antimicrobial activity to E. coli, S. aureus, P. aeruginosa, and C. albicans, and that the coatings with the additive exhibit over 99.99% reduction rate for the tested bacteria and fungi. The coating film is able to maintain over 99% antimicrobial reduction even after 1200 repeated solution wipings, or over 30 wash cycles of artificial sweat solution, indicating high durability. Furthermore, the yellowness of the coating is not evident (Δb < 2) despite the high loading of silver, and the silver nanoparticles have little impact on gloss, haze, and distinctness of the coating film image.

Decentralized wastewater treatment in an urban setting: a pilot study of the circulating fluidized bed bioreactor treating septic tank effluent.

To meet the increasing wastewater treatment demand while minimizing the land footprint of the treatment systems and plants, more efficient and compact processes are needed. The circulating fluidized bed bioreactor (CFBBR) has been proven to achieve high levels of biological nutrient removal. Past studies at the lab and pilot scale achieved 94% COD removal and 80% nitrogen removal at HRT's of 2-4 h. A collaborative project between Western University and the Guangzhou Institute of Energy Conversion (GIEC), in Guangzhou, China, further explored the treatment of municipal wastewater with the CFBBR. A pilot CFBBR, with aerobic and anoxic columns for nitrification and denitrification, was constructed at the GIEC for in-situ treatment of septic tank effluent from a residential building. Due to high concentrations of ammonia (NH4-N), the wastewater had a COD/N ratio of 2-3. Thus, operating at a longer HRT and supplementing COD, in the form of glucose, was necessary to achieve a high nitrogen removal efficiency. The system was run both with and without supplemental COD at HRT's between 16 and 21 h, treating approximately 1000-1270 L/d. Overall, a COD removal efficiency of at least 92%, ammonia removal of 97%, and nitrogen removal of 82% was achieved. The CFBBR system achieved an effluent with BOD and NH4-N concentrations both below 5 mg/L, a NO3-N concentration below 15 mg/L, and a total nitrogen concentration below 25 mg/L. The compact design of this pilot-CFBBR, coupled with its high BNR performance make it an excellent option for decentralized treatment of urban wastewaters.

A value-added step towards promoting the serviceability of fluidized bed bioreactor in treating wastewater with low carbon to nitrogen ratio.

Reusing microplastics and zeolite waste as free ammonia (FA)-mitigating carrier particle was proven a value-added step towards promoting the serviceability of fluidized bed bioreactor (FBBR) in treating wastewater with a low carbon to nitrogen ratio (i.e. C/N <3.0) in this study. Ammonia (NH4+) adsorption property capacitates zeolite as an FA mitigator. The microplastics and reused zeolite were processed into reused-zeolite/microplastic composite particle (RZ), whose merit of FA mitigation was fully developed via an optimally thermal modification to process modified-zeolite/microplastic particle (MZ). The 171-day biological nutrient removal (BNR) performance in a single integrated fluidized bed bioreactor (SIFBBR) shows that the bioreactor with MZ particle (SIFBBR-MZ) achieved nitrogen removal efficiency 10.0% higher than the bioreactor with RZ particle (SIFBBR-RZ) over the enhanced short-cut nitrification and denitrification. Analysis of microbial community structure unveils that the long-term lower FA inhibition favored more significant ammonia-oxidizing bacteria (AOB) enrichment and acclimated specific MZ biofilm predominant by nitrite (NO2-) denitrifier, contributing to the outperformance in nitrogen removal. Apart from fluidization energy conservation, the techno-economic analysis confirms that using MZ as an FA-mitigating carrier could be of great benefit for FBBR system: realizing waste utilization, reducing carbon addition and alleviating sludge treatment.

Protective effects of aerosolized pulmonary surfactant powder in a model of ventilator-induced lung injury.

Mechanical ventilation may contribute to the impairment of the pulmonary surfactant system, which is one of the mechanisms leading to the progression of acute lung injury. To investigate the potential protective effects of pulmonary surfactant in a rat model of ventilator-induced lung injury, the surfactant powder was aerosolized using an in-house made device designed to deliver the aerosolized powder to the inspiratory line of a rodent ventilator circuit. Rats were randomized to (i) administration of aerosolized recombinant surfactant protein C based pulmonary surfactant, (ii) intratracheally instillation of the same surfactant re-constituted in saline, and (iii) no treatment. Animals were monitored during 2 h of high-tidal volume mechanical ventilation, after which rats were sacrificed, and further analysis of lung mechanics and surfactant function were completed. Blood gas measurements during ventilation showed extended maintenance of oxygen levels above 400 mmHg in aerosol treated animals over non-treated and instilled groups, while total protein analysis showed reduced levels in the aerosol compared to non-treated groups. Dynamic captive bubble surface tension measurements showed the activity of surfactant recovered from aerosol treated animals is maintained below 1 mN/m. The prophylactic treatment of aerosolized surfactant powder reduced the severity of lung injury in this model.

Performance and bacterial community structure of a novel inverse fluidized bed bioreactor (IFBBR) treating synthetic municipal wastewater.

The performance of a lab-scale integrated anoxic and aerobic inverse fluidized bed bioreactors (IFBBR) for biological nutrient removal from synthetic municipal wastewater was studied at chemical oxygen demand (COD) loading rates of 0.34-2.10 kg COD/(m3-d) and nitrogen loading rates of 0.035-0.213 kg N/(m3-d). Total COD removal efficiencies of >84% were achieved, concomitantly with complete nitrification. The overall nitrogen removal efficiencies were >75%. Low biomass yields of 0.030-0.101 g VSS/g COD were achieved. Compared with other FBBR systems, the energy consumption for this IFBBR system was an average 59% less at organic loading rates (OLRs) of 1.02 and 2.10 kg COD/(m3-d). Bacterial community structures of attached and suspended biomass revealed that the dominant phyla were Proteobacteria, Bacteroidetes, and Epsilonbacteraeota, etc. The relative abundance of ammonia-oxidizing bacteria (AOBs) and nitrite-oxidizing bacteria (NOBs) in the aerobic attached biomass were 0.451% and 0.110%, respectively. COD mass balance in the anoxic zone was closed by consideration of sulfate reduction, which was confirmed by the presence of genus Chlorobium (sulfate-reducing bacteria) in the anoxic attached biofilm with a relative abundance of 0.32%.

Effective partial nitrification of ammonia in a fluidized bed bioreactor.

A lab-scale fluidized bed bioreactor with high-density polyethylene as biofilm carrier media was operated to study partial nitrification (PN) performance with high ammonia concentrations. The system was run at nitrogen loading rates (NLRs) from 1.2 to 4.8 kg N/(m3 d) with empty bed contact time of 2.0 and 2.7 h and four different influent ammonia concentrations of 100, 200, 300 and 400 mg/L. Dissolved oxygen concentration and temperature were maintained around 1.3 mg/L and 35°C, respectively. Stable PN was successfully achieved during the whole period with low effluent NO3-N concentration at less than 15 mg/L, due to effective suppression of nitrite-oxidizing bacteria activity at high concentrations of free ammonia (5.3-27.3 mg N/L) and low alkalinity-to-ammonia ratio. At the NLR of 3.6 kg N/(m3 d), NH4-N conversion and NO2-N accumulation ratios were 57.8% and 53.9%, respectively, which could be further used in the anaerobic ammonium oxidation process (ANAMMOX) as the effluent NO2-N/NH4-N ratio was 1.27.

Cold Bonding Method for Metallic Powder Coatings.

An efficient and simple method for preparing bonded metallic powder coating is in high demand in the paint manufacturing and application industries. The bonding purpose is to keep the mass percentage of metallic pigment consistent between the original and recycled coating powder, which aims at solving the problem of recyclability. One possible method capable of realizing this goal is using the binder to cohere metallic pigment with base particles through a cold bonding method. Through this approach, the pre-curing and high-reject-rate problems generally present in thermal bonding can be completely eliminated. In this paper, polyacrylic acid (PAA) and polyvinyl alcohol (PVA) are applied as binders for the bonding process. At various dosages of liquid binder and D.I. water, bonded samples with different bonding effect were prepared. Finally, a good bonding quality with the lowest variance between the mass concentrations of Al flakes in the original powder (before spray) and deposited powder (after spray) 2.94% with PAA as a binder and 0.46% with PVA as a binder was achieved. These results manifest that the cold bonding method is a green and simple approach for preparing the metallic powder coating.

Dry powder coated osmotic drug delivery system.

Dry powder coated osmotic drug delivery system (ODDS) were prepared and characterized using an innovative powder coating technology. Coating powder adhesion to the surface of the ODDS core was firstly performed through an electrostatic spray gun, followed by a curing step to allow those electrically deposited particles coalesce and form a continuous, uniform and strong coating film, which is the semipermeable membrane of the ODDS. Triethyl citrate (TEC) was found to be a better liquid plasticizer than PEG 400 both in reducing the glass transition temperature of the coating polymer (cellulose acetate) and in increasing the electrical conductivity of the ODDS cores, both of which led to an enhanced coating powder adhesion and film formation. Results of SEM indicated that the uniformity of the coating film varied significantly with the difference of curing time and temperature. Salbutamol sulfate and ibuprofen were used as the model drugs. Release profiles of both showed that zero-order drug release kinetics was achieved. Release rate of both drugs from powder coated ODDS could be adjusted by changing the coating level but was independent of the agitation speed and of the pH of the release media.

Bioaugmentation: An Emerging Strategy of Industrial Wastewater Treatment for Reuse and Discharge.

A promising long-term and sustainable solution to the growing scarcity of water worldwide is to recycle and reuse wastewater. In wastewater treatment plants, the biodegradation of contaminants or pollutants by harnessing microorganisms present in activated sludge is one of the most important strategies to remove organic contaminants from wastewater. However, this approach has limitations because many pollutants are not efficiently eliminated. To counterbalance the limitations, bioaugmentation has been developed and consists of adding specific and efficient pollutant-biodegrading microorganisms into a microbial community in an effort to enhance the ability of this microbial community to biodegrade contaminants. This approach has been tested for wastewater cleaning with encouraging results, but failure has also been reported, especially during scale-up. In this review, work on the bioaugmentation in the context of removal of important pollutants from industrial wastewater is summarized, with an emphasis on recalcitrant compounds, and strategies that can be used to improve the efficiency of bioaugmentation are also discussed. This review also initiates a discussion regarding new research areas, such as nanotechnology and quorum sensing, that should be investigated to improve the efficiency of wastewater bioaugmentation.

Emulsification Characteristics Using a Dynamic Woven Metal Microscreen Membrane.

An oscillatory emulsification system for the production of oil in water emulsions using a commercially available low-cost woven metal microscreen (WMMS) is investigated. The system allows for independent control of both the oscillation frequencies and amplitudes such that it provides two degrees of freedom for controlling the emulsion properties. The investigations included the production of both surfactant and particle-stabilized emulsions. The average droplet size was found to decrease when both the oscillation frequency and amplitude was increased. For surfactant-stabilized emulsions, using bi-surfactants in both the continuous and dispersed phases resulted in a smaller droplet size due to lower interfacial tension. For particle-stabilized emulsions, both the hydrodynamics of the system and the hydrophobic and hydrophilic nature of the stabilizing particles influenced the interfacial properties at the oil-water interface, which in turn affected the final droplet size and distribution with potential droplet breakage. In absence of the latter, a simple torque balance model can be used to reasonably predict the average emulsion droplet size.

Applying a novel electrostatic dry powder coating technology to pellets.

The present study aimed to apply a novel dry powder technology to coat pellets with different coating materials grounded into fine powders. Piroxicam, a non-steroidal anti-inflammatory drug, was used as the active pharmaceutical ingredient (API). Eudragit® EPO, Eudragit® RS/RL and Acryl EZE were used as the coating materials to achieve immediate release, sustained release and delayed release, respectively. Three steps including preheating, powder adhesion and curing were carried out to form the coating film while liquid plasticizers were used to decrease the glass transition temperature of coating powders and also served to reduce the electrical resistance of pellets. Results of SEM indicated coating film could be better formed by increasing curing temperature or extending curing time. Dissolution tests showed that three different drug release profiles, including immediate release, sustained release and delayed release, were achieved by this coating technology with different coating formulations. And the dry powder coated pellets using this developed technology exhibited an excellent stability with 1 month at 40 °C/75% RH. The coating procedure could be shortened to within 120 min and the use of fluidized hot air was minimized, both cutting down the overall cost dramatically compared to organic solvent coating and aqueous coating. All results demonstrated that the novel electrostatic dry powder coating method is a promising technology in the pharmaceutical coating industry.