Cumulative Deposition Research Articles

Challenging clinical management of a patient with Gaucher disease type IIIC homozygous for the D409H mutation, aortic valve calcification and porcelain aorta

Background. Gaucher disease is a rare lysosomal storage disorder caused by glucocerebrosidase enzyme deficiency resulting in the cumulative deposition of glucocerebroside in macrophages, predominantly effecting bone marrow, liver and spleen. Gaucher disease type IIIC is a rare subtype that is characterized by cardiovascular involvement, eye-movement disorders, and late-onset neurological symptoms. Case presentation. We present a 14-year-old adolescent boy diagnosed with Gaucher disease type IIIC at age four with a homozygous D409H mutation who developed severe aortic valve stenosis, extensive aortic calcification and a porcelain aorta despite enzyme replacement treatment since the diagnosis. Despite the challenges during the cardiac surgery, we successfully performed transcatheter aortic valve implantation (TAVI). The patient developed a complete atrioventricular block and required a pacemaker after the TAVI. He experienced further complications during the follow-up. Conclusion. The case presents the challenges in the treatment of cardiovascular complications in patients with Gaucher disease and demonstrates the importance of individualized treatment approaches, as well as the potential advantages and complications of TAVI in difficult situations like this.

Conazoles

Conazoles belong to the group of azole-based fungicides and pharmaceutical preparations that are widely used in agriculture for crop protection and in human and veterinary medicine for the treatment of oropharyngeal and urogenital mycotic infections. The antifungal mode of action consists in the inhibition of certain cytochrome c-oxidase enzymes leading to disruption of the ergosterol metabolic pathway, which plays a similar role in cholesterol synthesis in mammals. Some conazoles possess hepatotoxic properties, some are mutagenic and tumorigenic, some are only carcinogenic and some do not act in these negative ways. In addition, their potential for cumulative exposure and deposition of residues in the human body could contribute to an increased risk of certain diseases and adverse health conditions, particularly during the foetal development. For these reasons, the risk assessment of the use of conazoles in human medicine and plant protection requires harmonisation and further research.

HSPiP, Computational, and Thermodynamic Model-Based Optimized Solvents for Subcutaneous Delivery of Tolterodine Tartrate and GastroPlus‑Based In Vivo Prediction in Humans: Part II.

In part I, we reported Hansen solubility parameters (HSP, HSPiP program), experimental solubility at varied temperatures for TOTA delivery. Here, we studied dose volume selection, stability, pH, osmolality, dispersion, clarity, and viscosity of the explored combinations (I-VI). Ex vivo permeation and deposition studies were performed to observe relative diffusion rate from the injected site in rat skin. Confocal laser scanning microscopy (CLSM) study was conducted to support ex vivo findings. Moreover, GastroPlus predicted in vivo parameters in humans and the impact of various critical factors on pharmacokinetic parameters (PK). Immediate release product (IR) contained 60% of PEG400 whereas controlled release formulation (CR) contained PEG400 (60%), water (10%) and d-limonene (30%) to deliver 2mg of TOTA. GastroPlus predicted the plasma drug concentration of weakly basic TOTA as function of pH (from pH 2.0 to 9). The cumulative drug permeation and drug deposition were found to be in the order as B-VI˃ C-VI˃A-VI across rat skin. This finding was further supported with CLSM. Moreover, IR and CR were predicted to achieve Cmax of 0.0038µg/ mL and 0.00023µg/mL, respectively, after sub-Q delivery. Added limonene in CR extended the plasma drug concentration over period of 12h as predicted in GastroPlus. Parameters sensitivity analysis (PSA) assessment predicted that sub-Q blood flow rate is the only factor affecting PK parameters in IR formulation whereas this was insignificant for CR. Thus, sub-Q delivery CR would be promising alternative with ease of delivery to children and aged patient.

Evaluating the intake plugging effects on the electrical submersible pump (ESP) operating conditions using nodal analysis

The intake plugging of an electrical submersible pump (ESP) has presented a formidable challenge to conventional ESP wells. Attention to cumulative solid deposition is essential since it intensifies the intake plugging severity and impedes ESP performance. We present a new approach to evaluate the ESP performance degradation during increased intake plugging severity. In particular, we employ the intake plugging factor, rate-derating factor, and affinity law to calculate the new ESP speed at different plugging conditions. We used Schlumberger PIPESIM software to perform nodal analysis of the newly calculated ESP speed. The result was validated using the actual field data and compared to the field cases that reported the intake plugging issue. The nodal analysis showed a steady maximum ESP head with zero rate derating at the shut-in point. The intake plugging factor caused a significant reduction in the ESP operating rate and increased pump intake pressure and annulus liquid level. Based on the existing intake plugging field data, we established the quantitative standard for the normal and abnormal intake plugging factor range. The observed results agreed with the field downhole data recorded during the intake plugging problem. We identified that regulating the ESP speed to the reduced operating rate could minimize unexpected pump stoppage. It is also possible to carefully monitor the intake plugging problem by combining the annulus liquid level, the signature of pump intake pressure, and a deadhead test.

Quantifying pesticide emissions for drift deposition in comparative risk and impact assessment

Estimating emissions of chemical pesticides used in agriculture is an essential component in evaluating the potential toxicity-related impacts on humans and ecosystems in various comparative risk and impact assessment frameworks, such as life cycle assessment, environmental footprinting, absolute environmental sustainability assessment, chemical substitution, and risk prioritization. Emissions related to drift deposition—usually derived from drift experiments—can reach non-target areas, and vary as a function of crop characteristics and application technique. We derive cumulative drift deposition fractions for a wide range of experimental drift functions for use in comparative and mass-balanced approaches. We clarify that cumulative drift deposition fractions require to integrate the underlying drift functions over the relevant deposition area and to correct for the ratio of deposition area to treated field area to arrive at overall mass deposited per unit mass of applied pesticide. Our results show that for most crops, drift deposition fractions from pesticide application are below 0.03 (i.e. 3% of applied mass), except for grapes and fruit trees, where drift fractions can reach 5% when using canon or air blast sprayers. Notably, aerial applications on soybeans can result in significantly higher drift deposition fractions, ranging from 20% to 60%. Additionally, varying the nozzle position can lead to a factor of five differences in pesticide deposition, and establishing buffer zones can effectively reduce drift deposition. To address remaining limitations in deriving cumulative drift deposition fractions, we discuss possible alternative modelling approaches. Our proposed approach can be implemented in different quantitative and comparative assessment frameworks that require emission estimates of agricultural pesticides, in support of reducing chemical pollution and related impacts on human health and the environment.

Threatened European butterflies concentrate in areas of strong climatic change and atmospheric deposition pressure

Land use change, as a result of many local-scale decisions scaling up to large spatial extents, is considered the main threat to European butterflies. The impact of large-scale pressures, such as atmospheric nitrogen deposition or climate change, is less understood or less documented, respectively. However, it is acknowledged that they might reinforce the pressure on already threatened species. To evaluate the additional threat exerted by these pressures we compared their geographical pattern to those of threatened butterflies across Europe. We therefore derived range maps of 383 butterfly species and used two species-specific threat assessments derived from national and European Red Lists. We then used Spearman rank-correlations and beta-regressions to compare two metrics of species threat per 10 × 10 km raster cells with geographical patterns of cumulative nitrogen depositions from 1980 to 2015, as well as the magnitude of change in precipitation sums and temperature means between the decades 1979–1988 and 2004–2013. We found that threatened species tend to concentrate in areas with high nitrogen depositions and pronounced summer temperature changes. In particular, parts of central and eastern Europe were both hotspots of threatened butterflies and hotspots of climatic pressure. This spatial coincidence of the distribution of threatened butterfly species with large-scale patterns of nitrogen depositions and recent climate warming indicates an already considerable risk of regional to continental extinctions that will likely increase further in the future as climate change will most likely intensify. Consequences for area-based conservation measures are discussed.

Valorization to hydrogen of bio-oil aqueous fractions from lignocellulosic biomass pyrolysis by aqueous phase reforming over Pt/C catalyst

Aqueous phase reforming was studied for the valorization to hydrogen of the aqueous fraction of bio-oil from lignocellulosic biomass pyrolysis. Aqueous phase reforming was carried out at 220 °C with a 3 % wt. Pt/carbon catalyst and an aqueous fraction of bio-oil feed containing 1 % wt. of organic matter. Binary and multicomponent mixtures representing aqueous fractions of bio-oil were studied. Strong hydrogen production dependence on aqueous fraction of bio-oil composition was evidenced. Higher processability was obtained for aqueous fractions of bio-oil rich in levoglucosan and hydroxyacetone, reaching a hydrogen production close to 40 mmol per gram of organic carbon, whereas furfural and acetic acid hampered reforming. A significant influence of minority components such as methanol and, particularly, formic acid, was observed. These components improved reforming of the whole multicomponent mixture, showing that blending with biorefinery fractions rich in them can improve the applicability of aqueous phase reforming. The catalyst exhibited stable activity and hydrogen production after 5 reaction cycles and more than 20 h. An increase in selectivity was observed during cycles 2 and 3, which was studied by characterization of fresh and used catalysts to show structure-selectivity relationships. No significant variation of Pt2+/Pt0 and metal particle mean diameter were observed, but Pt nanoparticles underwent morphological changes leading to higher prevalence of low coordination sites, in particular step-edge sites on the particle surface, resulting in higher hydrogen production. Temperature programmed desorption and oxidation analysis showed a cumulative deposition of reaction byproducts on the catalyst surface that contributed to loss of activity.

Modeling the Seasonal Variation of Windborne Transmission of Porcine Reproductive and Respiratory Syndrome Virus between Swine Farms.

Modeling the windborne transmission of aerosolized pathogens is challenging. We adapted an atmospheric dispersion model named the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model to simulate the windborne dispersion of porcine reproductive and respiratory syndrome virus (PRRSv) between swine farms and incorporated the findings into an outbreak investigation. The risk was estimated semi-quantitatively based on the cumulative daily deposition of windborne particles and the distance to the closest emitting farm with an ongoing outbreak. Five years of data (2014:2018) were used to study the seasonal differences of the deposition thresholds of the airborne particles containing PRRSv and to evaluate the model in relation to risk prediction and barn air filtration. When the 14-day cumulative deposition was considered, in winter, above-threshold particle depositions would reach up to 30 km from emitting farms with 84% of them being within 10 km. Long-distance pathogen transmission was highest in winter and fall, lower in spring, and least in summer. The model successfully replicated the observed seasonality of PRRSv, where fall and winter posed a higher risk for outbreaks. Reaching the humidity and temperature thresholds tolerated by the virus in spring and summer reduced the survival and infectivity of aerosols beyond 10-20 km. Within the data limitations of voluntary participation, when wind was assumed to be the sole route of PRRSv transmission, the predictive performance of the model was fair with >0.64 AUC. Barn air filtration was associated with fewer outbreaks, particularly when exposed to high levels of viral particles. This study confirms the usefulness of the HYSPLIT model as a tool when determining seasonal effects and distances and informs the near real-time risk of windborne PRRSv transmission that can be useful in future outbreak investigations and for implementing timely control measures.

Sediment sink-source transitions in the middle and lower reaches of the Yangtze River estuary

Human activities have severely altered the Yangtze River (Changjiang) Estuary’s pattern, beach-trough shape, and delta in recent decades. Existing research has studied the sediment “source–sink” relationship between the Yangtze River mainstream and estuary using gauged suspended sediment data. This method overestimated the decline in the suspended sediment concentration in the estuary, as riverbed scouring or deposition have not filtered out amounts related to sand mining or waterway dredging. This study took the Yangtze River Basin as the research subject and used spot observed runoff, sediment, and riverbed topography data gathered between 1980 and 2020 to analyze the sediment trapping effect of the Three Gorges Reservoir (TGR) and study the “source-sink” relationship of suspended sediment transport in the middle-lower reaches of the Yangtze River. The Yangtze Estuary Delta is dominated by scouring, which shows an increasing trend. During the operation of the TGR (2003–2020), the suspended sediment load entering the Yangtze Estuary from the Yangtze River mainstream decreased by 68% compared to the amount prior to operation commencing (1960–2002). However, studies have found that there are still large amounts of bottom sand with riverbed load movement characteristics after the operation of the Three Gorges Project and that riverbed souring of the downstream dam has increased the degree of deposition recharge. The amount of sediment in the Yangtze Estuary decreased between 2003 and 2018 compared with the period 1981 to 2002, with an annual decrease of 16.9%. The cumulative deposition of the Yichang–Datong and Datong–Xuliujing reaches from 1981–2002 was 3.13×108 m3 and 1.60×108 m3, respectively, and cumulative scouring from 2002–2018 was 28.52×108 m3 and 16.01×108 m3. This study concluded that even if the suspended sediment load entering the estuary decreased significantly after the operation of the TGR, the riverbed in the middle-lower reaches of the Yangtze River has gradually transformed from the “sink” of sediment deposition to the “source” of sediment supply.

Development of Miconazole-Loaded Microemulsions for Enhanced Topical Delivery and Non-Destructive Analysis by Near-Infrared Spectroscopy.

The antifungal drug miconazole nitrate has a low solubility in water, leading to reduced therapeutic efficacy. To address this limitation, miconazole-loaded microemulsions were developed and assessed for topical skin delivery, prepared through spontaneous emulsification with oleic acid and water. The surfactant phase included a mixture of polyoxyethylene sorbitan monooleate (PSM) and various cosurfactants (ethanol, 2-(2-ethoxyethoxy) ethanol, or 2-propanol). The optimal miconazole-loaded microemulsion containing PSM and ethanol at a ratio of 1:1 showed a mean cumulative drug permeation of 87.6 ± 5.8 μg/cm2 across pig skin. The formulation exhibited higher cumulative permeation, permeation flux, and drug deposition than conventional cream and significantly increased the in vitro inhibition of Candida albicans compared with cream (p < 0.05). Over the course of a 3-month study conducted at a temperature of 30 ± 2 °C, the microemulsion exhibited favorable physicochemical stability. This outcome signifies its potential suitability as a carrier for effectively administering miconazole through topical administration. Additionally, a non-destructive technique employing near-infrared spectroscopy coupled with a partial least-squares regression (PLSR) model was developed to quantitatively analyze microemulsions containing miconazole nitrate. This approach eliminates the need for sample preparation. The optimal PLSR model was derived by utilizing orthogonal signal correction pretreated data with one latent factor. This model exhibited a remarkable R2 value of 0.9919 and a root mean square error of calibration of 0.0488. Consequently, this methodology holds potential for effectively monitoring the quantity of miconazole nitrate in various formulations, including both conventional and innovative ones.

The Evolution of Historic Agroforestry Landscape in the Northern Apennines (Italy) and Its Consequences for Slope Geomorphic Processes

Historic agricultural practices have played a dominant role in shaping landscapes, creating a heritage which must be understood and conserved from the perspective of sustainable development. Agroforestry (i.e., the practice of combining trees with agriculture or livestock) has existed since ancient times in European countries, and it has been recognised as one of the most resilient and multifunctional cultural landscapes, providing a wide range of economic, sociocultural, and environmental benefits. This research explores aspects of the history, physical characteristics, decline, and current state of conservation of historic agroforestry systems on the Northern Apennines in Italy, using an interdisciplinary approach combining archival sources, landscape archaeology, dendrochronology, and GIS analysis. Furthermore, through computer-based modelling, this research aims to evaluate how the abandonment of this historic rural land-use strategy impacted slope geomorphic processes over the long term. The importance of environmental values attached to traditional rural landscapes has received much attention even beyond the heritage sector, justifying the definition of transdisciplinary approaches necessary to ensure the holistic management of landscapes. Through the integration of the Unit Stream Power-Based Erosion Deposition (USPED) equation with landscape archaeological data, the paper shows how restoring the historic agroforestry landscape could significantly mitigate soil mass movements in the area. Thus, the interdisciplinary workflow proposed in this study enables a deep understanding of both the historical evolution of agroforestry systems and its resulting effects for cumulative soil erosion and deposition in the face of climate change.

Polycyclic aromatic hydrocarbons (PAHs) in air, foliage, and litter in a subtropical forest: Spatioseasonal variations, partitioning, and litter-PAH degradation

Forest canopies play a vital role in scavenging airborne semi-volatile organic compounds. The present study measured polycyclic aromatic hydrocarbons (PAHs) in the understory air (at two heights), foliage, and litterfall in a subtropical rainforest (the Dinghushan mountain) in southern China. ∑17PAH concentrations in the air ranged from 2.75 to 44.0 ng/m3 (mean = 8.91 ng/m3), showing a spatial variation depending on the forest canopy coverage. Vertical distributions of the understory air concentrations also indicated PAH inputs from the above-canopy air. The concentrations of PAHs in fresh litter (with a mean of 261 ± 163 ng/g dry weight (dw)) were slightly lower than those in the foliage (362 ± 291 ng/g dw). Unlike the stable air PAH concentrations for most of the time of the year, the temporal variations of foliage and litter concentrations were remarkable but generally similar. Higher or comparable leaf/litter-air partition coefficients (KLA) in fresh litter compared with living KLA in leaves suggest that the forest litter layer is an efficient storage media for PAHs. Degradation of three-ring PAHs in litter under the field conditions follows first-order kinetics (R2 = 0.81), while the degradation is moderate for four-ring PAHs and insignificant for five- and six-ring PAHs. The yearly net cumulative deposition of PAHs through forest litterfall in the whole Dinghushan forest area over the sampling year was about 1.1 kg, 46% of the initial deposition (2.4 kg). This spatial variations study provides the results of in-field degradation of litter PAHs and makes a quantitative assessment of the litter deposition of PAHs, deducing their residence dynamics in the litter layer in a subtropical rainforest.

Long-term concentration of tropical forest nutrient hotspots is generated by a central-place apex predator

Apex predators typically affect the distribution of key soil and vegetation nutrients through the heterogeneous deposition of prey carcasses and excreta, leading to a nutrient concentration in a hotspot. The exact role of central-place foragers, such as tropical raptors, in nutrient deposition and cycling, is not yet known. We investigated whether harpy eagles (Harpia harpyja) in Amazonian Forests—a typically low soil fertility ecosystem—affect soil nutrient profiles and the phytochemistry around their nest-trees through cumulative deposition of prey carcasses and excreta. Nest-trees occurred at densities of 1.5–5.0/100 km2, and each nest received ~ 102.3 kg of undressed carcasses each year. Effects of nests were surprisingly negative over local soil nutrient profiles, with soils underneath nest-trees showing reductions in nutrients compared with controls. Conversely, canopy tree leaves around nests showed significant 99%, 154% and 50% increases in nitrogen, phosphorus and potassium, respectively. Harpy eagles have experienced a 41% decline in their range, and many raptor species are becoming locally extirpated. These are general examples of disruption in biogeochemical cycles and nutrient heterogeneity caused by population declines in a central-place apex predator. This form of carrion deposition is by no means an exception since several large raptors have similar habits.

Ecological impacts of the industrial revolution in a lowland raised peat bog near Manchester, NW England.

(1) Ombrotrophic peat bogs provide valuable records of environmental change on long timescales but are rarely preserved near the major centers of industrial activity. Holcroft Moss is a rare example of a stratigraphically intact lowland peat bog in NW England, which provides a valuable opportunity to trace industrial impacts on vegetation in a sensitive environmental archive close to the early industrializing cities of Manchester and Liverpool. (2) We reconstructed environmental changes at Holcroft Moss before and after the Industrial Revolution using a decadal-scale record of pollen, non-pollen palynomorphs, microcharcoal, peat composition (organic content and ash-free bulk density) and heavy metal content, constrained by a radiocarbon and SCP (spheroidal carbonaceous particle) chronology. We examine the relationship between abiotic and biotic environmental tracers using principal component analysis and evaluate the role of local and regional climatic and anthropogenic drivers using canonical redundancy analysis and partitioning of variation. (3) Results show significant changes in bog vegetation composition during the last 700 years. Prior to 1750 CE, climate and agro-pastoral activity (grazing and fires) were the main drivers of vegetation change. Subsequently, regional coal-fired industry contributed to major increases in atmospheric pollutants (dust, heavy metals, and acid deposition) that severely impacted vegetation, driving the decline of Sphagnum. Grasses rose to dominance in the 20th century associated especially with bog conversion and cumulative nitrogen deposition. Although atmospheric pollution significantly decreased in the post-industrial era, vegetation has not returned to pre-industrial conditions, reflecting the ongoing impact of global change drivers which pose challenges for conservation and restoration. (4) Synthesis. Paleoecological studies are needed to reveal the long-term history of vegetation degradation and to offer guidelines for restoration and conservation practices. This study reconstructs the last 700 years of a peat bog located between Manchester and Liverpool, revealing the timing and nature of vegetation changes across the trajectory of early industrialization and eventual post-industrial decline. Our study reveals the progressive dominance of regional anthropogenic forcing and highlights that the present-day vegetation does not have past analogs within the last 700 years. Conservation measures favoring the reintroduction of Sphagnum are justified in redressing the major biological legacy of the Industrial Revolution, while steps to increase Calluna should also be considered in light of its resilience to dry and fire-prone conditions.

Preparation of Conotoxin-Encapsulated Chitosan Nanoparticles and Evaluation of Their Skin Permeability.

μ-Conotoxin CnIIIC (conotoxin, CTX)-loaded chitosan nanoparticles (CTX-NPs) were prepared using the ionic cross-linking method. The CTX-NPs were spherical and well with a polydispersity index of 0.292 ± 0.039, drug loading efficiency of 25.9 ± 1.2%, and encapsulation efficiency of 95.6 ± 1.3%. In vitro release studies showed that the release behavior of CTX-NPs in a pH 5.0 acetate buffer followed zero-order kinetics. In vitro transdermal experiments using Franz diffusion cells mounted with mouse abdominal skin demonstrated that the cumulative intradermal deposition amount of CTX per unit area in 8h (D8) and permeability coefficient (Pf) of CTX loaded on CTX-NPs were 2.30- and 7.71-times that of the CTX solution. In vivo transdermal experiments in mice showed that the amount of CTX deposited in the skin after 8h of CTX saline administration was significantly lower than that of CTX deposited in the skin after administration of CTX-NPs. In vitro fluorescence labeling transdermal studies through Franz diffusion cells mounted with mouse abdominal skin indicated that CTX-NPs aggregated at hair follicles. Skin irritation tests in mice indicated that the irritation due to CTX-NPs was negligible. The cytotoxicity experiment showed that the viability of Balb/c 3T3 cells with CTX-NPs containing 230μg/mL (0.08μM) CTX was greater than 75%. CTX-NPs increase intradermal deposition of CTX by accumulating in hair follicles, which has positive implications for transdermal penetration of CTX.

Modeling demonstrates minimal ecological risks of cuttings discharges associated to oil and gas drilling with deep water wells

To assess the impacts of drill cutting discharges in the Gulf of Mexico, a particle dispersion modeling study was conducted on hypothetical drilling scenarios. The goal was to assess cumulative seabed deposition, and potential hydrocarbon loading from non-aqueous drilling fluids (NADF). Cuttings drilled with NADF showed to have minimal impact on local fauna at the deep-water well simulated. A hypothetical drill site was modeled under 3 different seasonally representative met-ocean conditions. The site is located approximately 260 km from the coast in water roughly 3500 meters (m) deep. Cumulative deposition was assessed for all materials released, whereas hydrocarbon loading was assessed based on the potential for NADF fluids to be retained on cuttings. Smothering effects on the benthic community are not anticipated. Hydrocarbon deposition was also very limited, ≤165 ppm of TPH. Overall, the cuttings drilled with NADF are predicted to have minimal impact on local fauna.

Targeted drug delivery with polydisperse particle transport and deposition in patient-specific upper airway during inhalation and exhalation

Identifying the deposition pattern of inhaled pharmaceutical aerosols in the human respiratory system and understanding the effective parameters in this process is vital for more efficient drug delivery to this region. This study investigated aerosol deposition in a patient-specific upper respiratory airway and determined the deposition fraction (DF) and pressure drop across the airway. An experimental setup was developed to measure the pressure drop in the same realistic geometry printed from the patient-specific geometry. The unsteady simulations were performed with a flow rate of 15 L/min and different particle diameters ranging from 2 to 30 µm. The results revealed significant flow circulation after the nasal valve in the upper and oropharynx regions, and a maximum local velocity observed in the nasopharynx. Transient cumulative deposition fraction showed that after 2 s of the simulation, all particles deposit or escape the computational domain. About 30 % of the injected large particles (dp ≥ 20 µm) deposited in the first 1 cm away from the nostril and more than 95 % deposited in the nasal airway before entering the oropharynx region. While almost 94 % deposition in trachea was composed of particles smaller than 5 µm. Approximately 20 % of inhaled fine particles (2–5 µm) deposited in the upper airway and the rest deposited in oropharynx, larynx and trachea.

Protein corona mediated liposomal drug delivery for bacterial infection management

Liposomes have been widely investigated as a class of promising antibiotic delivery systems for the treatment of life-threatening bacterial infections. However, the inevitable formation of protein corona on the liposomal surface can heavily impact in vivo performance. A better understanding of the effects of protein corona on liposomal behavior can significantly improve antibacterial liposomal drug development. Here, the critical role of protein corona in mediating liposome-bacteria interactions was elucidated. Adsorption of negatively charged protein on cationic liposome weakened electrostatic attraction-enhanced liposomal binding to the bacteria. Cumulative complement deposition on anionic liposome composed of phosphatidylglycerol (DSPG sLip) contributed to a superior binding affinity of DSPG sLip to planktonic bacteria and biofilms, which was exploited to enhance bacteria-targeted drug delivery. In both S. aureus-related osteomyelitis and pneumonia mice models, DSPG sLip was demonstrated as a promising antibiotic nanocarrier for managing MRSA infection, indicating the benefits of lipid composition-based protein corona modulation in liposomal antibiotic delivery for bacterial infection treatment.

Compressibility and Rarefaction Effects on Particle Dynamics and Heat Transfer in Aerosol Deposition Process

The aerosol deposition (AD) method is an emerging coating technique to create a dense ceramic or metal layer on a substrate through the kinetic impaction and cumulative deposition of ultrafine solid particles under near-vacuum conditions. Prediction of the particles’ impact velocity and temperature during the AD process is crucial in enhancing the coating quality. In the present work, a two-way coupled Eulerian-Lagrangian model is developed for an AD system equipped with a converging-barrel nozzle to simulate the supersonic gas flow, particle in-flight behavior, as well as particle conditions upon impact on a flat substrate. The focus of the current study is to understand the effects of compressibility and rarefaction on particle velocity and temperature during the AD process. The effects of compressibility and rarefaction can be assessed using the Mach and Knudsen numbers. Therefore, different models for the drag coefficient and the heat transfer coefficient that take into account the Knudsen, Mach, and Reynolds number effects are implemented into the computational fluid dynamics (CFD) models. The results show that compressibility and rarefaction have significant influence on the particle temperature and velocity. As the particle size reduces, the effects of compressibility and rarefaction become more important.

Inhibition of MAD2L1 Mediates Pulmonary Fibrosis through Impairment of Mitochondrial Function and Induction of Cell Senescence.

Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible, and progressive interstitial lung disease characterized by recurrent alveolar epithelial cell injury, fibroblast hyperproliferation, and cumulative deposition of extracellular matrix leading to alveolar destruction in the lungs. Mitotic arrest deficient 2 like 1 (MAD2L1) is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at metaphase and is a potential therapeutic target in cancers. However, the role of MAD2L1 in pulmonary fibrosis has not been explored. We analyzed the expression of MAD2L1 in lung tissues from control subjects, IPF patients, and mice with bleomycin-induced fibrosis via IHC, qRT-PCR, and Western blot analysis. We examined the roles of MAD2L1 in ROS production, mitochondrial function, cell senescence, and the establishment of a profibrotic microenvironment. We found that MAD2L1 was highly upregulated in alveolar epithelial cells in fibrotic lung tissues from both patients with IPF and mice with bleomycin-induced fibrosis. Loss of MAD2L1 expression or activity led to decreases of cell viability and proliferation in A549 cells. Subsequent mechanistic investigation demonstrated that inhibition of MAD2L1 damaged mitochondria, which led to augmented ROS production and cellular senescence, and thus promoted the establishment of a profibrotic microenvironment. Taken together, these results reveal that alleviation of alveolar epithelial cell mitochondrial damage arising from augmentation of MAD2L1 may be a novel therapeutic strategy for mitigating pulmonary fibrosis.