Adsorption-desorption of Atrazine with 9 Agricultural Soils in China.

In this work, the characteristics and mechanisms for atrazine adsorption-desorption with 9 types of soils were investigated with batch equilibrium studies, elemental analyses, infrared spectroscopy, and UV‒visible spectroscopy. The atrazine sorption data for the 9 soils showed better fits with the Freundlich model than the Langmuir model, except with Red earth in Jiangxi (REJ) The results showed that the adsorption capacity was positively correlated with the organic matter (OM) content and negatively correlated with cation-exchange capacity (CEC) and pH. UV‒visible spectroscopy showed that dissolved organic matter (DOM) in the soil enhanced atrazine adsorption, but the adsorption on different DOM fractions was quite different. In addition, the infrared spectra revealed differences in the functional groups of soils and these functional groups may drive the adsorption process via hydrogen bonding and coordination with the -NH2 groups in atrazine.

Paroxetine induced larva zebrafish cardiotoxicity through inflammation response.

Paroxetine (PRX) is a common antidepressant drug which widely existence in natural environment. Numerous studies in the past few decades have focused on the beneficial effects of PRX on depression, however, the toxic properties and the potential mechanisms remain unclear. In this study, zebrafish embryos were exposed to 1.0, 5.0, 10 and 20 mg/L of PRX from 4 to 120-hour-post-fertilization (hpf), and it showed that PRX exposure caused adverse effects in zebrafish embryos, including decreased body length, blood flow velocity, cardiac frequency, cardiac output and increased burst activity and atria area. Meanwhile, the Tg (myl7: EGFP) and Tg (lyz: DsRed) transgenic zebrafish were used to detect the cardiotoxicity and inflammation response of PRX. Moreover, the heart development associated genes (vmhc, amhc, hand2, nkx2.5, ta, tbx6, tbx16 and tbx20) and inflammatory genes (IL-10, IL-1ß, IL-8 and TNF-α) were up-regulated after PRX challenge. In addition, Aspirin was used to alleviate the PRX-induced heart development disorder. In conclusion, our study verified the PRX induced inflammatory related cardiotoxicity in larva zebrafish. Meanwhile, the current study shown the toxic effects of PRX in aquatic organism, and provide for the environmental safety of PRX.

TMBPF-induced neurotoxicity and oxidative stress in zebrafish larvae: impacts on central nervous system development and dopamine neurons.

Bisphenol A (BPA), a common bisphenol molecule, is well known in the environment as an endocrine disruptor. Furthermore, BPs (BPA, BPS, BPF, and BPAF) have been shown in recent years to be neurotoxic to zebrafish. Tetramethyl bisphenol F (TMBPF) has recently been introduced as a substitute for bisphenol A (BPA) in various industries, including plastics and food contact coatings. However, a growing number of studies have demonstrated that the toxicity of some BPA substitutes is similar to or even stronger than BPA, posing potential harm to human health and the environment. In this study, we used zebrafish larvae as a model to investigate the neurodevelopmental effects of TMBPF at different concentrations (0, 0.25, 0.5, 1, 2, 4 and 8 mg/L). Our results showed that exposure to TMBPF at concentrations higher than 4 mg/L for 72 h post-fertilization (hpf) resulted in zebrafish mortality, whereas exposure to 2 mg/L for 144 hpf caused deformities. Furthermore, TMBPF exposure inhibited the development of the central nervous system, motor nerves, and dopamine neurons in zebrafish. Real-time polymerase chain reaction (PCR) analysis revealed that TMBPF exposure significantly down-regulated the expression of oxidative stress-related genes (Cu/Zn-SOD, Mn-SOD, and CAT) and neurodevelopmental genes (mbp, gafp, and syn2a), while up-regulated the expression of dopamine-related genes (th1, th2, and dat). Notably, treatment with the antioxidant N-acetylcysteine (NAC) alleviated TMBPF-induced toxicity. NAC can regulate the expression of genes related to oxidative stress, neurodevelopment and dopamine development, and make the nerve development of zebrafish normal. Overall, our research suggested that TMBPF may disrupt the development of the early central nervous system and dopamine neurons, leading to abnormal motor behavior in zebrafish larvae. These results highlight the potential risks associated with the use of TMBPF in various industries and the importance to evaluate its potential risks to human health and the environment.

Human Rhinovirus Infection of the Respiratory Tract Affects Sphingolipid Synthesis.

The 17q21 asthma susceptibility locus includes asthma risk alleles associated with decreased sphingolipid synthesis, likely resulting from increased expression of ORMDL3. ORMDL3 inhibits serine-palmitoyl transferase (SPT), the rate-limiting enzyme of de novo sphingolipid synthesis. There is evidence that decreased sphingolipid synthesis is critical to asthma pathogenesis. Children with asthma and 17q21 asthma risk alleles display decreased sphingolipid synthesis in blood cells. Reduced SPT activity results in airway hyperreactivity, a hallmark feature of asthma. 17q21 asthma risk alleles are also linked to childhood infections with human rhinovirus (RV). This study evaluates the interaction of RV with the de novo sphingolipid synthesis pathway, and the alterative effects of concurrent SPT inhibition in SPT-deficient mice and human airway epithelial cells. In mice, RV infection shifted lung sphingolipid synthesis gene expression to a pattern that resembles genetic SPT deficiency, including decreased expression of Sptssa, a small SPT subunit. This pattern was pronounced in lung epithelial cellular adhesion molecule (EpCAM+) cells and reproduced in human bronchial epithelial cells. RV did not affect Sptssa expression in lung CD45+ immune cells. RV increased sphingolipids unique to the de novo synthesis pathway in mouse lung and human airway epithelial cells. Interestingly, these de novo sphingolipid species were reduced in the blood of RV-infected wild-type mice. RV exacerbated SPT deficiency-associated airway hyperreactivity. Airway inflammation was similar in RV-infected wild-type and SPT-deficient mice. This study reveals the effects of RV infection on the de novo sphingolipid synthesis pathway, elucidating a potential mechanistic link between 17q21 asthma risk alleles and rhinoviral infection.

The Role of Biochar in Reducing the Bioavailability and Migration of Persistent Organic Pollutants in Soil-Plant Systems: A Review.

The amendment of biochar in soils contaminated with persistent organic pollutants (POPs) is an environmentally friendly in situ remediation measure. Numerous studies focused on the application of biochars to reduce the uptake of POPs by plants in soils. In this review, we summarized the role of biochar in reducing the migration of POPs in soil-plant systems. The mechanisms of biochar reducing the bioavailability of POPs in the soil, i.e. immobilization and promoted biodegradation, and the influencing factors are fully discussed. Especially in rhizosphere amended with biochar, the synergistic effect of POPs-root exudates-microorganisms on the reduced bioavailability of POPs is analyzed. This paper suggests that future researches should focus on the long-term environmental fate of POPs sorbed on high-temperature biochars and the long-term impacts of low-temperature biochars on the interaction of POPs-root exudates-rhizosphere microorganisms. All the above are necessary for efficient and safe use of biochar for remediating POP-contaminated farmland soils.

Respiratory Syncytial Virus (RSV) Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology.

UNLABELLED: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, which causes high rates of morbidity and mortality in infants and the elderly. Models of human RSV pulmonary disease are needed to better understand RSV pathogenesis and to assess the efficacy of RSV vaccines. We assessed the RSV-specific human innate, humoral, and cellular immune responses in humanized mice (mice with a human immune system [HIS mice]) with functional human CD4(+) T and B cells. These mice were generated by introduction of HLA class II genes, various human cytokines, and human B cell activation factor into immunodeficient NOD scid gamma (NSG) mice by the use of an adeno-associated virus vector, followed by engraftment of human hematopoietic stem cells. During the first 3 days of infection, HIS mice lost more weight and cleared RSV faster than NSG mice. Human chemokine (C-C motif) ligand 3 (CCL3) and human interleukin-1ß (IL-1ß) expression was detected in the RSV-infected HIS mice. The pathological features induced by RSV infection in HIS mice included peribronchiolar inflammation, neutrophil predominance in the bronchioalveolar lavage fluid, and enhanced airway mucus production. Human anti-RSV IgG and RSV-neutralizing antibodies were detected in serum and human anti-RSV mucosal IgA was detected in bronchioalveolar lavage fluid for up to 6 weeks. RSV infection induced an RSV-specific human gamma interferon response in HIS mouse splenocytes. These results indicate that human immune cells can induce features of RSV lung disease, including mucus hyperplasia, in murine lungs and that HIS mice can be used to elicit human anti-RSV humoral and cellular immunity. IMPORTANCE: Infections with respiratory syncytial virus (RSV) are common and can cause severe lung disease in infants and the elderly. The lack of a suitable animal model with disease features similar to those in humans has hampered efforts to predict the efficacy of novel anti-RSV therapies and vaccines for use in humans. A murine model consisting of mice with a human immune system (HIS mice) could be useful for assessment of RSV disease and anti-RSV responses specific to humans. This study investigates an HIS mouse model to imitate human RSV disease and immune responses. We found that RSV lung infection in HIS mice results in an RSV-specific pathology that mimics RSV disease in humans and induces human anti-RSV immune responses. This model could be useful for better understanding of human RSV disease and for the development of RSV therapies.

Developing and evaluating a machine-learning-based algorithm to predict the incidence and severity of ARDS with continuous non-invasive parameters from ordinary monitors and ventilators.

OBJECTIVES: Major observational studies report that the mortality rate of acute respiratory distress syndrome (ARDS) is close to 40%. Different treatment strategies are required for each patient, according to the degree of ARDS. Early prediction of ARDS is helpful to implement targeted drug therapy and mechanical ventilation strategies for patients with different degrees of potential ARDS. In this paper, a new dynamic prediction machine learning model for ARDS incidence and severity is established and evaluated based on 28 parameters from ordinary monitors and ventilators, capable of dynamic prediction of the incidence and severity of ARDS. This new method is expected to meet the clinical practice requirements of user-friendliness and timeliness for wider application. METHODS: A total of 4738 hospitalized patients who required ICU care from 159 hospitals are employed in this study. The models are trained by standardized data from electronic medical records. There are 28 structured, continuous non-invasive parameters that are recorded every hour. Seven machine learning models using only continuous, non-invasive parameters are developed for dynamic prediction and compared with methods trained by complete parameters and the traditional risk adjustment method (i.e., oxygenation saturation index method). RESULTS: The optimal prediction performance (area under the curve) of the ARDS incidence and severity prediction models built using continuous noninvasive parameters reached0.8691 and 0.7765, respectively. In terms of mild and severe ARDS prediction, the AUC values are both above 0.85. The performance of the model using only continuous non-invasive parameters have an AUC of 0.0133 lower, in comparison with that employing a complete feature set, including continuous non-invasive parameters, demographic information, laboratory parameters and clinical natural language text. CONCLUSIONS: A machine learning method was developed in this study using only continuous non-invasive parameters for ARDS incidence and severity prediction. Because the continuous non-invasive parameters can be easily obtained from ordinary monitors and ventilators, the method presented in this study is friendly and convenient to use. It is expected to be applied in pre-hospital setting for early ARDS warning.

Satellite cloud image segmentation based on lightweight convolutional neural network.

More than 50% of the images captured by optical satellites are covered by clouds, which reduces the available information in the images and seriously affects the subsequent applications of satellite images. Therefore, the identification and segmentation of cloud regions come to be one of the most important problems in current satellite image processing. Due to the complexity and variability of satellite images, especially when the ground is covered with snow, the boundary information of cloud regions is difficult to be accurately identified. The fast and accurate segmentation of cloud regions is a difficult point in the current research. We propose a lightweight convolutional neural network. Firstly, channel attention is used to optimize the effective information in the feature maps as a way to improve the network's ability to extract semantic information at each scale. Then, we fuse high and low-dimensional feature maps to enhance the network's ability to obtain small-scale semantic information. In addition, the feature aggregation module automatically adjusts the input multi-level feature weights to highlight the details of different features. Finally, we design the fully connected conditional random field to solve the problem that some noise in the input image and local minima during training is passed to the output layer resulting in the loss of edge features. Experimental results show that the proposed method achieves 0.9695 and 0.8218 for overall accuracy and recall, respectively, which has higher segmentation accuracy with the shortest time consumption compared with other state-of-the-art methods.

Hydrothermal conversion of Cd/Zn hyperaccumulator (Sedum alfredii) for heavy metal separation and hydrochar production.

The harmless treatment of heavy metal-enriched hyperaccumulator biomass is the main barrier to the industrialization of phytoremediation. Hydrothermal conversion of Sedum alfredii using different solvents (i.e ·H2O and HCl) at 210-300 â„ƒ was performed to investigate the behaviors of Cd and Zn, and the characteristics and potential application of the derived hydrochars were determined. Low temperature and HCl addition favored the removal of Cd/Zn from the solid phase. The highest removal efficiencies of Cd (95.0%) and Zn (89.3%) were achieved at 210 â„ƒ with the presence of HCl. The yield, pH, ash content, element concentration, functional groups, and crystalline minerals of the derived hydrochar were influenced by the reaction temperature and addition of HCl. The leaching risk of Cd and Zn was significantly reduced by hydrothermal conversion. The addition of HCl facilitated the immobilization of Zn, while it enhanced the mobility of Cd. Moreover, the hydrochar derived at 210 â„ƒ showed increased sorption capacity towards Cu, and the addition of HCl greatly improved the energy density of hydrochar. These results suggest that HCl-mediated hydrothermal conversion could be a promising technique to achieve the separation of Cd and Zn from hyperaccumulator biomass as well as the production of value-added hydrochar.

Hydrothermal carbonization of garden waste by pretreatment with anaerobic digestion to improve hydrohcar performance and energy recovery.

Sustainable and resourceful utilization of garden waste with high lignocellulosic content remains a huge challenge, anaerobic digestion (AD) and hydrothermal treatment provide prospective technologies with achieving environmental and economic benefits. In this study, a 7-28 d AD was provided as a biomass pretreatment means and combined with hydrothermal carbonization (HTC) to treat three typical garden wastes (leaves, branches, grass). The results showed that AD pretreatment could effectively change the surface composition and structure properties of the feedstocks and thus modulating the properties of the hydrochar downstream. Compared to the unpretreatment samples, the specific surface area (SSA), higher heating value (HHV), energy density and nutrient elements (P and K) of hydrochar obtained by AD pretreatment were significantly improved and enriched, respectively. Specifically, the highest HHV of hydrochar obtained from leaves, branches, and grass were 25.71, 25.63, and 23.81 MJ/kg, which obtained with 21, 14, and 7 d of AD pretreatment respectively. The P contents of hydrochar of leaves and grass pretreated with AD for 14 and 7 d were 205% and 15% higher than those without AD pretreatment, respectively. Additionally, in this coupled system, the biomass energy recovery of 90.2% (78.2% biochar and 12.0% CH4) was achieved on leaves pretreated with AD for 21 d. Energy recovery of 81.2% (66.8% biochar, 14.4% CH4) and 71.3% (39.7% biochar, 31.6% CH4) was obtained by 14 d of AD pretreatment on branches and grass, respectively. Thus, this study enhances energy utilization efficiency and reduces secondary waste generation, providing valuable new insights into AD coupled with HTC technology.

Dietary long-chain omega 3 fatty acids modify sphingolipid metabolism to facilitate airway hyperreactivity.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are essential nutrients that can affect inflammatory responses. While n-3 PUFAs are generally considered beneficial for cardiovascular disease and obesity, the effects on asthma, the most common inflammatory lung disease are unclear. While prenatal dietary n-3 PUFAs decrease the risk for childhood wheezing, postnatal dietary n-3 PUFAs can worsen allergic airway inflammation. Sphingolipid metabolism is also affected by dietary n-3 PUFAs. Decreased sphingolipid synthesis leads to airway hyperreactivity, besides inflammation, a cardinal feature of asthma, and common genetic asthma risk alleles lead to lower sphingolipid synthesis. We investigated the effect of dietary n-3 PUFAs on sphingolipid metabolism and airway reactivity. Comparing a fish-oil diet with a high n-3 PUFA content (FO) to an isocaloric coconut oil-enriched diet (CO), we found an n-3 PUFA-dependent effect on increased airway reactivity, that was not accompanied by inflammation. Lung and whole blood content of dihydroceramides, ceramides, sphingomyelins, and glucosylceramides were lower in mice fed the n-3 PUFA enriched diet consistent with lower sphingolipid synthesis. In contrast, phosphorylated long chain bases such as sphingosine 1-phosphate were increased. These findings suggest that dietary n-3 PUFAs affect pulmonary sphingolipid composition to favor innate airway hyperreactivity, independent of inflammation, and point to an important role of n-3 PUFAs in sphingolipid metabolism.

The third heart sound after exercise in athletes: an exploratory study.

The purpose of our study was to investigate the frequency of the third heart sound (S3) of athletes after exercise, and to determine whether the frequency and amplitude of S3 were related to cardiac function. The phonocardiogram exercise test (PCGET) was used in this study, and healthy volunteers consisting of 84 athletes (age 21.0±1.7 years; 62 males and 22 females) and 45 non-athletes (age 24.1±2.0 years; 33 males and 12 females) were enrolled. All subjects were healthy except one with a cardiac murmur without known cause. Immediately after exercise, S3 occurred in 21 athletes (25.0%) and 10 non-athletes (22.2%) during PCGET. There were very significant differences between pre-exercise and post-exercise in the frequency of S3 (P<0.01), and no significant difference between athletes and nonathletes (P>0.05). The prevalence of S3/S2≥1 was significantly (P<0.05) higher for the athlete group (47.1%) as compared to the non-athlete group (10%). Those results indicated that the emergence of S3 was an indicator of heart burden, and S3 after exercise in the athlete group was physiological. Our study showed that the amplitude of S3 had a very sensitive response to cardiac function reduction and S3/S2≥1 could eventually be used to assess cardiac fatigue states.

Comparative evaluation on municipal sewage sludge utilization processes for sustainable management in Tibet.

In recent years, a sharp increase in the amount of municipal sewage sludge (MSS) in Tibet has posed serious threats to the fragile ecological environment. Tibetan sludge, with a high content of volatile and low heavy metals, has re-utilization advantages, and thus, the selection of appropriate utilization processes for Tibetan MSS is of great importance. In this study, not only the processes themselves, but also other factors including legislations and environmental pollution were investigated. This study introduced the current waste management legislation situation (especially for MSS) in China and Tibet, China. Moreover, a series of SWOT (strength & weakness and opportunity & threats) analyses were conducted to compare anaerobic digestion (AD), incineration, pyrolysis (PY), gasification, and anaerobic digestion coupled with pyrolysis. The results showed that anaerobic digestion coupled with pyrolysis was the optimal treatment option, because anaerobic digestion was suitable for the low oxygen content in Tibet. Although only 50-60% of the organic matter in MSS could be degraded by anaerobic digestion, the residual organic matter (energy) could be further decomposed by pyrolysis, converting it into pyrolytic gas, bio-oil, and biochar, as valuable products. Sludge digestate pyrolysis could reduce environmental risks, save energy, recover materials, and produce high value-added materials. Moreover, it provides a "zero waste" solution for sludge disposal and promotes a "Circular Economy." The challenges and obstacles of MSS anaerobic digestion coupled with pyrolysis in Tibet were also investigated. This study provides an important technical reference for the comprehensive utilization of Tibetan MSS.

Potential of yak dung-derived hydrochar as fertilizer: Mechanism and model of controlled release of nitrogen.

Improving fertilizer efficiency with assistance of biochar has drawn much attention in sustainable agriculture. Promoting slow-release properties of biochar itself with cost-effective production technology is a pressing demand. In this study, hydrochar derived from nutrition-enriched yak dung (HC) and corresponding controlled release nitrogen fertilizer (HCRNF) via HCl modifying were studied, and the slow release performance as well as mechanisms were investigated. The results show that HCRNF presents a better N controlled-release performance with cumulative N release amounts of 56.01%-70.30% compared with 72.60%-78.45% of HC. The specific surface area reached highest 47.161 m2·g-1 in HCRNFs with the pore volume of 0.098 cm3·g-1. Hydrochloric acid modification treatment increases the surface acid group contents such as phenolic hydroxyl group content increasing to 1.48 mmol·g-1 in HCRNF250. Because the porous structure and stable internal force between N and O-containing functional groups are improved, the N desorption from HCRNF is retarded, which shows a controlled release behavior. We concluded that the HCRNF via HCl modification in this work has a great application potential as slow released N fertilizer in sustainable green agriculture.

Bioaccumulation of Pyraoxystrobin and Its Predictive Evaluation in Zebrafish.

This paper aims to understand the bioaccumulation of pyraoxystrobin in fish. Using a flow-through bioconcentration method, the bioconcentration factor (BCF) and clearance rate of pyraoxystrobin in zebrafish were measured. The measured BCF values were then compared to those estimated from three commonly used predication models. At the exposure concentrations of 0.1 µg/L and 1.0 µg/L, the maximum BCF values for pyraoxystrobin in fish were 820.8 and 265.9, and the absorption rate constants (K1) were 391.0 d-1 and 153.2 d-1, respectively. The maximum enrichment occurred at 12 d of exposure. At the two test concentrations, the clearance rate constant (K2) in zebrafish was 0.5795 and 0.4721, and the half-life (t1/2) was 3.84 d and 3.33 d, respectively. The measured BCF values were close to those estimated from bioconcentration predication models.

Interactive effect of dissolved organic matter and phenanthrene on soil enzymatic activities.

The investigation of dissolved organic matter (DOM) on urease, catalase and polyphenol oxidase activity in a phenanthrene (Phe)-contaminated soil was conducted under laboratory incubation conditions. Values of soil enzymatic activity depended mainly on incubation time. In the initial 16 days, urease activity increased, and was followed by a decrease. In the initial 8 days, catalase activity decreased and then increased. Variation of polyphenol oxidase activity was just the reverse of catalase activity. After 30 days of incubation, no pronounced difference among treatments with Phe, Phe and DOM, and control were detected in urease, catalase and polyphenol oxidase activity. Phe might inhibit urease and catalase, and stimulate polyphenol oxidase. DOM could improve inhibition of Phe in soil urease and catalase activity during the initial period of applying DOM. Nevertheless, DOM had no significant effect on polyphenol oxidase activity in the Phe contaminated soil. There was a negative correlation between catalase and polyphenol oxidase (r = -0.761***), and catalase and urease (r = -0.554**). Additionally, a positive correlation between polyphenol oxidase and urease was also detected (r = 0.701***). It is implied that the formed DOM after application of organic wastes into soils may counteract the inhibition of polycyclic aromatic hydrocarbons in soil enzyme activities.

Acute toxicity of fluazinam to aquatic organisms and its bioaccumulation in Brachydanio rerio.

Fluazinam (FZN) is a dinitroaniline fungicide. To evaluate the environmental risk of FZN in aquatic environments and ascertain the potential danger to typical aquatic organisms in China, the acute toxicity of FZN to representative aquatic organisms, including Brachydanio rerio, Chlorella vulgaris Beij., Daphnia magna Straus, and Xenopus laevis, was measured, and its bioaccumulation properties in Brachydanio rerio were further investigated. The results showed that the acute toxicity of FZN to Brachydanio rerio and Xenopus laevis is extremely high, and the bioaccumulation factor BCF8d of FZN in Brachydanio rerio ranges between 2287 and 3570, implying that it has high bioaccumulation properties. FZN poses a strong environmental risk for aquatic organisms and possesses great bioaccumulation properties, which may cause pollution to aquatic environments.

Neonatal Genetic Delivery of Anti-Respiratory Syncytial Virus (RSV) Antibody by Non-Human Primate-Based Adenoviral Vector to Provide Protection against RSV.

Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infection in infants. Immunoprophylaxis with the anti-RSV monoclonal antibody, palivizumab, reduces the risk for RSV-related hospitalizations, but its use is restricted to high-risk infants due to the high costs. In this study, we investigated if genetic delivery of anti-RSV antibody to neonatal mice by chimpanzee adenovirus type 7 expressing the murine form of palivizumab (AdC7αRSV) can provide protection against RSV. Intranasal and intramuscular administration of AdC7αRSV to adult mice resulted in similar levels of anti-RSV IgG in the serum. However, only intranasal administration resulted in detectable levels of anti-RSV IgG in the bronchoalveolar lavage fluid. Intranasal administration of AdC7αRSV provided protection against subsequent RSV challenge. Expression of the anti-RSV antibody was prolonged following intranasal administration of AdC7αRSV to neonatal mice. Protection against RSV was confirmed at 6 weeks of age. These data suggest that neonatal genetic delivery of anti-RSV antibody by AdC7αRSV can provide protection against RSV.

Post-exposure immunization by capsid-modified AdC7 vector expressing Pseudomonas aeruginosa OprF clears P. aeruginosa respiratory infection.

Respiratory infections with Pseudomonas aeruginosa are major health problems, particularly in patients with cystic fibrosis (CF). No vaccine against P. aeruginosa is yet available. A vaccine that controls colonization of the respiratory tract with P. aeruginosa could be useful to prevent chronic infection and exacerbations. Replication-deficient adenoviral (Ad) vectors based on non-human serotypes are attractive vaccine platforms as they can circumvent the problem of pre-existing anti-Ad immunity in humans. The primate-based AdC7 vector AdC7OprF.RGD that expresses the outer membrane protein F (OprF) of P. aeruginosa (AdC7OprF) and that displays an integrin-binding arginine-glycine-aspartic acid (RGD) sequence is a potent inducer of lung mucosal and protective immunity. Here, we investigated the efficacy of immunization with AdC7OprF.RGD to clear an already established P. aeruginosa respiratory infection in mice (wild-type and CF) and rats. Intratracheal administration of the clinical P. aeruginosa strain RP73 embedded in agar beads was used to establish persistent infection. Subsequent intranasal immunization with AdC7OprF.RGD induced robust P. aeruginosa-specific systemic and mucosal, humoral and cellular immune responses. Importantly, the AdC7OprF.RGD immunized mice effectively cleared P. aeruginosa from the lungs. Likewise, immunization with AdC7OprF.RGD of CF mice and Sprague Dawley rats with established P. aeruginosa respiratory infection showed enhanced anti-Pseudomonas immune responses and increased clearance of P. aeruginosa from the lungs. These data suggest that AdC7OprF.RGD can be effective as a post-exposure vaccine and may be useful in clinical settings in particular for patients with CF who frequently harbor the bacteria over prolonged periods.

The fermentation product 2,3-butanediol alters P. aeruginosa clearance, cytokine response and the lung microbiome.

Diseases that favor colonization of the respiratory tract with Pseudomonas aeruginosa are characterized by an altered airway microbiome. Virulence of P. aeruginosa respiratory tract infection is likely influenced by interactions with other lung microbiota or their products. The bacterial fermentation product 2,3-butanediol enhances virulence and biofilm formation of P. aeruginosa in vitro. This study assessed the effects of 2,3-butanediol on P. aeruginosa persistence, inflammatory response, and the lung microbiome in vivo. Here, P. aeruginosa grown in the presence of 2,3-butanediol and encapsulated in agar beads persisted longer in the murine respiratory tract, induced enhanced TNF-α and IL-6 responses and resulted in increased colonization in the lung tissue by environmental microbes. These results led to the following hypothesis that now needs to be tested with a larger study: fermentation products from the lung microbiota not only have a role in P. aeruginosa virulence and abundance, but also on the increased colonization of the respiratory tract with environmental microbes, resulting in dynamic shifts in microbiota diversity and disease susceptibility.