Immunological corollary of the pulmonary mycobiome in bronchiectasis:The Cameb study

Understanding the composition and clinical importance of the fungal mycobiome was recently identified as a key topic in a “research priorities” consensus statement for bronchiectasis. Patients were recruited as part of the CAMEB study: an international multicentre cross-sectional Cohort of Asian and Matched European Bronchiectasis patients. The mycobiome was determined in 238 patients by targeted amplicon shotgun sequencing of the 18S–28S rRNA internally transcribed spacer regions ITS1 and ITS2. Specific quantitative PCR for detection of and conidial quantification for a range of airway Aspergillus species was performed. Sputum galactomannan, Aspergillus specific IgE, IgG and TARC (thymus and activation regulated chemokine) levels were measured systemically and associated to clinical outcomes. The bronchiectasis mycobiome is distinct and characterised by specific fungal genera, including Aspergillus, Cryptococcus and Clavispora. Aspergillus fumigatus (in Singapore/Kuala Lumpur) and Aspergillus terreus (in Dundee) dominated profiles, the latter associating with exacerbations. High frequencies of Aspergillus-associated disease including sensitisation and allergic bronchopulmonary aspergillosis were detected. Each revealed distinct mycobiome profiles, and associated with more severe disease, poorer pulmonary function and increased exacerbations. The pulmonary mycobiome is of clinical relevance in bronchiectasis. Screening for Aspergillus-associated disease should be considered even in apparently stable patients.MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Published versio

Water quality assessment in the rivers along the water conveyance system of the Middle Route of the South to North Water Transfer Project (China) using multivariate statistical techniques and receptor modeling

A total of 190 grab water samples were collected from 19 rivers along the water conveyance system of the Middle Route of China\u27s interbasin South to North Water Transfer Project (MRSNWTP). Multivariate statistics including principal component/factor analysis (PCA/FA), analysis of variance (ANOVA), and cluster analysis (CA) were employed to assess water quality, and the receptor model of factor analysis-multiple linear regression (FA-MLR) was used for source identification/apportionment of pollutants from natural processes and anthropogenic activities to river waters. Our results revealed that river waters were primarily polluted by CODMn, BOD, NH4+-N, TN, TP, and Cd with remarkably spatio-temporal variability, and there were increasing industrial effluents in rivers northward. FA/PCA identified four classes of water quality parameters, i.e., mineral composition, toxic metals, nutrients, and organic pollutants. CA classified the selective 19 rivers into three groups reflecting their varying water pollution levels of moderated pollution, high pollution, and very high pollution. The FA-MLR receptor modeling revealed predominantly anthropogenic inputs to river solutes in Beijing and Tianjin, i.e., 77% of nitrogen and 90% of phosphorus from industry, and 80% of CODMn from domestics. This study is critical for water allocation and division in the water-receiving areas using the existing rivers for MRSNWTP

Assessment of soil heavy metals for eco-environment and human health in a rapidly urbanization area of the upper Yangtze Basin

Abstract Soil pollution with heavy metals (HMs) has been attracting more and more interests, however, assessment of eco-environmental and human risks particularly in a rapidly urbanization area (the upper Yangtze) remains limited. Multiple modern indices were firstly performed for complete risk assessment of eco-environment and human health based on a high-spatial-resolution sampling. Averages of HMs were far below grade II threshold level of the Chinese Environmental Quality standards for soils, whereas Cd, As and Hg considerably exceeded the local background values. EF suggested overall moderate enrichments of Cd and Se, resulting in soils uncontaminated to moderately contaminated with them. Potential ecological risk index showed significant differences among Counties that were characterized by moderate risk. However, several sites were moderately to heavily contaminated with As, Cd and Hg by Igeo, resulting in that these sites were categorized as “considerable risk”, or “high risk”. Moreover, children were more susceptible to the potential health risk irrespective of the carcinogenic or non – carcinogenic risk. There were no significant carcinogenic and non – carcinogenic risks for adults, children however showed significant non – carcinogenic effect. Our first assessment provided important information for policy making to reduce the potential effects of soil contamination on human and eco-environment

Challenges of COVID-19 vaccination in patients with cancer

Patients with cancer are at increased risk of SARA-CoV-2 infection or developing severe COVID-19 cases due to malignancy or immunosuppressive therapy, but they are generally excluded from the target population for COVID-19 vaccination. In general, inactivated vaccines are safe and immunogenic for patients with cancer, but live attenuated vaccines are not recommended. The study suggested that the safety of the mRNA COVID-19 vaccine in patients with cancer is similar to that in healthy people, but immunogenicity is slightly weaker, and a booster dose may be needed. This paper aims to summarize the results of COVID-19 vaccine clinical studies conducted in patients with cancer worldwide and the relevant guidelines released by authorities, so as to provide evidence for promoting COVID-19 vaccination for patients with cancer

Challenges of COVID-19 vaccination in patients with cancer

Patients with cancer are at increased risk of SARA-CoV-2 infection or developing severe COVID-19 cases due to malignancy or immunosuppressive therapy, but they are generally excluded from the target population for COVID-19 vaccination. In general, inactivated vaccines are safe and immunogenic for patients with cancer, but live attenuated vaccines are not recommended. The study suggested that the safety of the mRNA COVID-19 vaccine in patients with cancer is similar to that in healthy people, but immunogenicity is slightly weaker, and a booster dose may be needed. This paper aims to summarize the results of COVID-19 vaccine clinical studies conducted in patients with cancer worldwide and the relevant guidelines released by authorities, so as to provide evidence for promoting COVID-19 vaccination for patients with cancer

Precision immunization: a new trend in human vaccination

Vaccination has been one of the major revolutions in the history of human health. Vaccination programs have targeted entire populations such as infants or elderly subjects as a matter of being efficient with time and resources. These general populations are heterogeneous in terms of factors such as ethnicity, health status, and socio-economics. Thus, there have been variations in the safety and effectiveness profiles of certain vaccinations according to current population-wide strategies. As the concept of precision medicine has been raised in recent years, many researchers have suggested that vaccines could be administered more precisely in terms of particular target populations, vaccine formulations, regimens, and dosage levels. This review addresses the concept and framework of precision immunization, summarizes recent and representative clinical trials of among specific populations, mentions important factors to be addressed in customizing vaccinations, and provides suggestions on the establishment of precision immunization with the goal of maximizing the effectiveness of vaccines in general

Safety and immunogenicity of a novel quadrivalent subunit influenza vaccine in animal models

Background: Compared with trivalent influenza vaccines, quadrivalent influenza vaccines are expected to provide wider protection against influenza B virus infections. We developed a novel quadrivalent subunit influenza vaccine which was distinct from the influenza vaccines available on the market in production process. In this research, we evaluated the safety and immunogenicity of the quadrivalent subunit influenza vaccine in animal models. Methods: In toxicity assessment, 40 SD rats were randomly assigned to be intramuscularly injected with 1.0 ml of the tested vaccine (33 μg/ml) or 0.9% sodium chloride solution. In irritation assessment, eight rabbits were randomly assigned to receive 0.5 ml of tested vaccine or phosphate buffer solution intramuscularly. Thirty-two guinea pigs were randomly assigned to be intramuscularly injected with high-dose tested vaccine (0.5 ml), low-dose tested vaccine (0.05 ml), ovalbumin, or 0.9% sodium chloride solution, respectively, for sensitization assessment. In immunogenicity assessment, 50 BALB/c mice were equally randomized to receive one dose of tested vaccine, two doses of tested vaccine with an interval of 14 days, 0.5 ml of trivalent subunit influenza vaccine, 0.5 ml of monovalent subunit influenza vaccine, or 0.5 ml of phosphate buffer solution. Orbital blood was collected before and 28 and 42 days after administration of the injections for detecting influenza antibody titers. Results: No abnormal toxicity and irritation in rats and rabbits showed in the gross autopsy and histopathological examinations. The results of sensitization in guinea pigs indicated that no obvious allergic symptoms observed in the high-dose and low-dose vaccine groups within 30 min after twice provocations, and the result of sensitization evaluation was negative. Vaccine induced significant immune responses in mice with 100% seroconversion rates at 28 and 42 days after the first dose. The geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies at day 28 in one-dose quadri–vaccine and two-dose quadri–vaccine groups were comparable to those in the tri–vaccine or mono-vaccine groups for shared influenza strains. However, the GMTs of HI antibodies against H1N1 (P = 0.025) and BV (P = 0.049) at day 42 in one-dose quadri–vaccine group were significantly lower than those in the tri–vaccine or mono-vaccine groups. The GMTs of HI antibodies against H1N1, H3N1, BY, and BV at day 28 and day 42 were comparable between one-dose quadri–vaccine and two-dose quadri–vaccine groups. Conclusions: The quadrivalent subunit influenza vaccine was safe and immunogenic in animal models. One dose of the vaccine could elicit a satisfactory antibody response in mice

Study on the Optimal Design for Cavitation Reduction in the Vortex Suction Cup for Underwater Climbing Robot

In order to adhere to the wall stably in an underwater environment, a vortex suction cup that injects high-pressure water inside via two axisymmetrically side-distributed inlets to create a negative pressure area in the center is the necessary component for the underwater climbing robot (UCR). However, the suction force of this vortex suction cup is reduced and periodically unstable due to unstable cavitation. The aim of this paper is to propose a cavitation reduction optimization method for vortex suction cups and to verify the effectiveness of the optimization. Analyses of this vortex flow, including streamlines, pressure, and cavitation number fluctuations, were carried out by the introduced computational fluid dynamics (CFD) simulating methods based on the multiphase RNG k−ε model to study the periodic fluctuations of the suction force of the original suction cup and the optimized ones. Force measurement and vortex observation experiments were conducted to compare the suction force of the original vortex suction cup and the optimized suction cup, as well as the cavitation and pressure fluctuation phenomenon. Results of simulation and experiments prove the existence of the effect of vortex cavitation on the suction performance and verify the rationality of optimization as well

Structural Basis for the Regiospecificity of a Lipase from <i>Streptomyces</i> sp. W007

The efficiency and accuracy of the synthesis of structural lipids are closely related to the regiospecificity of lipases. Understanding the structural mechanism of their regiospecificity contributes to the regiospecific redesign of lipases for meeting the technological innovation needs. Here, we used a thermostable lipase from Streptomyces sp. W007 (MAS1), which has been recently reported to show great potential in industry, to gain an insight into the structural basis of its regiospecificity by molecular modelling and mutagenesis experiments. The results indicated that increasing the steric hindrance of the site for binding a non-reactive carbonyl group of TAGs could transform the non-specific MAS1 to a α-specific lipase, such as the mutants G40E, G40F, G40Q, G40R, G40W, G40Y, N45Y, H108W and T237Y (PSI > 80). In addition, altering the local polarity of the site as well as the conformational stability of its composing residues could also impact the regiospecificity. Our present study could not only aid the rational design of the regiospecificity of lipases, but open avenues of exploration for further industrial applications of lipases