Store-operated calcium entry enhances the polarization and chemotaxis of neutrophils in the peripheral venous blood of patients with bronchial asthma by upregulating ERM protein.

Background: Neutrophils can be rapidly recruited and are largely abundant in the airways of patients with asthma. However, whether the polarization and chemotaxis of neutrophils in patients with asthma are abnormal, and the underlying mechanisms, have not been clarified. Pseudopods formation is the initial step of neutrophils' polarization, ezrin, radixin and moesin (ERM) play an important role in the polarization of neutrophils. As an important signaling molecule in cell physiological processes, Ca2+ has been shown to be involved in the polarity changes of neutrophils. This study thus aimed to explore polarization and chemotaxis of neutrophils in patients with asthma and the underlying mechanism. Methods: Fresh neutrophils were isolated using standard separation protocols. The polarization and chemotactic activity of neutrophils were observed using Zigmond chamber and Transwell migration assay under linear concentration gradients of N-formyl-methionine-leucine-phenylalanine (fMLP) or interleukin (IL)-8. The distribution of calcium, ERMs and F-actin in neutrophils were observed by confocal laser scanning microscope. The expression of the main components of ERMs (moesin and ezrin) was detected with reverse transcription-polymerase chain reaction (RT-PCR). Results: Compared with those in the healthy control group, the polarization and chemotaxis of neutrophils in the venous blood of patients with asthma were significantly increased, and the expression and distribution of cytoskeletal proteins F-actin and ezrin were abnormal. The expression and function of key components of store-operated calcium entry (SOCE), stromal interaction molecule 1 (STIM1), STIM2, and Orai1 of neutrophils in patients with asthma were significantly increased. Conclusions: The polarization and chemotaxis of neutrophils in the venous blood of patients with asthma are increased. This may be due to the abnormal expression and distribution of ERM and F-actin as a result of abnormal SOCE function.

Abnormal neutrophil polarization in chronic obstructive pulmonary disease and how cigarette smoke extracts attract neutrophils.

Background: Airway inflammation produced by neutrophils is a critical factor in the development of chronic obstructive pulmonary disease (COPD). Poor or excessive neutrophil polarization and chemotaxis may lead to pathogen accumulation and tissue damage. However, it is unclear how cigarette smoke extract (CSE) attracts neutrophils and to what extent COPD is affected by the improper polarization of these abnormal neutrophils. This study sought to assess the polarization and migration dynamics of neutrophils isolated from patients with different severities of COPD compared to healthy smoking and non-smoking control subjects, and to detect how CSE triggers the polarization of neutrophils. Methods: The neutrophils were freshly isolated using standard isolation protocol. The polarization of the neutrophils was observed using a Zigmond chamber when stimulated by a linear concentration gradient of CSE or N-formyl-methionine-leucine-phenylalanine (fMLP). Confocal laser-scanning microscopy was used to observe the intracellular calcium of the neutrophils. The experimental data are presented as the mean ± standard deviation. SPSS 20.0 software was used for the statistical analysis. A P value <0.05 was considered statistically significant. Results: The neutrophils from the COPD patients showed a higher frequency of spontaneous polarization and a lower prevalence of directionality polarization than those from the healthy control (HC) and smoker subjects. The abnormal polarization of the neutrophils from the COPD patients was altered by the influence of store-operated calcium entry (SOCE) component matrix interaction molecules 1 and 2 and calcium release-activated calcium channel protein 1 [stromal interaction molecule 1 (STIM1), Stromal interaction molecule 2 (STIM2), and calcium release-activated calcium modulator 1 (ORAI1)]. Conclusions: The COPD neutrophils exhibited unique polarization and migration patterns compared to those of the cells examined from other populations. The attraction of CSEs to neutrophils was mediated by the SOCE/Akt/Src pathway.

Terahertz spectroscopy of citrate Salts: Effects of crystalline state and crystallization water.

Citrate salts are widely used as food additives and medicines for health and treatment. Accurate and fast detection of citrate salts is most important in food industry and medicine health. In this work, terahertz (THz) time-domain spectroscopy was used to detect and analyze different citrate salts and differentiate their crystalline hydrates. Effects of the crystalline state, the crystallization water and the metal cation on the THz spectra of citrate salts were investigated. Results indicate the crystalline states of the citrate salt samples strongly influence their THz featuring absorption peaks and citrate salts with crystallization water have larger absorption coefficients at the same frequency and higher possibility of existing featuring absorption peaks in comparison with citrate salts without crystallization water. Size of the metal cation also influences the THz absorption peak of the citrate salt and a small cation radius results in a large absorption peak frequency. This work illustrates the terahertz spectroscopy can be well used as a new technique to detect the citrate salts and differentiate their crystalline hydrates.

Fine-Scale Space-Time Cluster Detection of COVID-19 in Mainland China Using Retrospective Analysis.

Exploring spatio-temporal patterns of disease incidence can help to identify areas of significantly elevated or decreased risk, providing potential etiologic clues. The study uses the retrospective analysis of space-time scan statistic to detect the clusters of COVID-19 in mainland China with a different maximum clustering radius at the family-level based on case dates of onset. The results show that the detected clusters vary with the clustering radius. Forty-three space-time clusters were detected with a maximum clustering radius of 100 km and 88 clusters with a maximum clustering radius of 10 km from 2 December 2019 to 20 June 2020. Using a smaller clustering radius may identify finer clusters. Hubei has the most clusters regardless of scale. In addition, most of the clusters were generated in February. That indicates China's COVID-19 epidemic prevention and control strategy is effective, and they have successfully prevented the virus from spreading from Hubei to other provinces over time. Well-developed provinces or cities, which have larger populations and developed transportation networks, are more likely to generate space-time clusters. The analysis based on the data of cases from onset may detect the start times of clusters seven days earlier than similar research based on diagnosis dates. Our analysis of space-time clustering based on the data of cases on the family-level can be reproduced in other countries that are still seriously affected by the epidemic such as the USA, India, and Brazil, thus providing them with more precise signals of clustering.

Study of the Effects of Air Pollutants on Human Health Based on Baidu Indices of Disease Symptoms and Air Quality Monitoring Data in Beijing, China.

There is an increasing body of evidence showing the impact of air pollutants on human health such as on the respiratory, and cardio- and cerebrovascular systems. In China, as people begin to pay more attention to air quality, recent research focused on the quantitative assessment of the effects of air pollutants on human health. To assess the health effects of air pollutants and to construct an indicator placing emphasis on health impact, a generalized additive model was selected to assess the health burden caused by air pollution. We obtained Baidu indices (an evaluation indicator launched by Baidu Corporation to reflect the search popularity of keywords from its search engine) to assess daily query frequencies of 25 keywords considered associated with air pollution-related diseases. Moreover, we also calculated the daily concentrations of major air pollutants (including PM10, PM2.5, SO2, O3, NO2, and CO) and the daily air quality index (AQI) values, and three meteorological factors: daily mean wind level, daily mean air temperature, and daily mean relative humidity. These data cover the area of Beijing from 1 March 2015 to 30 April 2017. Through the analysis, we produced the relative risks (RRs) of the six main air pollutants for respiratory, and cardio- and cerebrovascular diseases. The results showed that O3 and NO2 have the highest health impact, followed by PM10 and PM2.5. The effects of any pollutant on cardiovascular diseases was consistently higher than on respiratory diseases. Furthermore, we evaluated the currently used AQI in China and proposed an RR-based index (health AQI, HAQI) that is intended for better indicating the effects of air pollutants on respiratory, and cardio- and cerebrovascular diseases than AQI. A higher Pearson correlation coefficient between HAQI and RRTotal than that between AQI and RRTotal endorsed our efforts.

Medical resource preparation and allocation for humanitarian assistance based on module organization.

BACKGROUND: This research aims to associate the allocation of medical resources with the function of the modular organization and the possible needs for humanitarian assistance missions. METHODS: The overseas humanitarian medical assistance mission, which was sent after a disaster on the hospital ship Peace Ark, part of China's People's Liberation Army (PLA) Navy, was considered as study model. The cases used for clustering and matching sample formation were randomly selected from the existing information related to Peace Ark's mission. RESULTS: Categories of the reusable resources clustered by this research met the requirement of the actual consumption almost completely (more than 95%) and the categories of non-reusable resources met the requirement by more than 80%. In the mission's original resource preparing plan, more than 30% of the non-reusable resource categories remained unused during the mission. In the original resource preparing plan, some key non-reusable resources inventories were completely exhausted at the end of the mission, while 5% to 30% of non-reusable resources remained in the resource allocation plan generated by this research at the end of the mission. CONCLUSIONS: The medical resource allocation plan generated here can enhance the supporting level for the humanitarian assistance mission. This research could lay the foundation for an assistant decision-making system for humanitarian assistance mission.

Transfection of bone marrow mesenchymal stem cells using green fluorescence protein labeled hVEGF165 recombinant plasmid mediated by liposome.

OBJECTIVE: To study the role of bone marrow mesenchymal stem cells (BMSCs) in construction of vascularized engineered tissue. METHODS: hVEGF165 was amplified via RT-PCR before recombinant with pShuttle- green fluorescence protein;green fluorescent protein (GFP)-CMV. Then the recombinant shuttle plasmid was transfected into BMSCs with Lipofectamine(TM) 2000 for packaging and amplifying. hVEGF165 mRNA expression in BMSCs cells was tested. RESULTS: The sequence of hVEGF165 in pShuttle-GFP-hVEGF165 plasmid was confirmed by double-enzyme cleavage method and sequencing. hVEGF165 was highly expressed in BMSCs. CONCLUSIONS: The GFP/hVEGF165 recombinant plasmid vector was constructed successfully and expressed effectively in host cells, which may be helpful for discussing the possibility of the application of VEGF165-BMSCs in tissue engineering and ischemic disease cure.

The novel H1N1 Influenza A global airline transmission and early warning without travel containments.

A novel influenza A (H1N1) has been spreading worldwide. Early studies implied that international air travels might be key cause of a severe potential pandemic without appropriate containments. In this study, early outbreaks in Mexico and some cities of United States were used to estimate the preliminary epidemic parameters by applying adjusted SEIR epidemiological model, indicating transmissibility infectivity of the virus. According to the findings, a new spatial allocation model totally based on the real-time airline data was established to assess the potential spreading of H1N1 from Mexico to the world. Our estimates find the basic reproductive number R0 of H1N1 is around 3.4, and the effective reproductive number fall sharply by effective containment strategies. The finding also implies Spain, Canada, France, Panama, Peru are the most possible country to be involved in severe endemic H1N1 spreading.

Risk analysis for the highly pathogenic avian influenza in Mainland China using meta-modeling.

A logistic model was employed to correlate the outbreak of highly pathogenic avian influenza (HPAI) with related environmental factors and the migration of birds. Based on MODIS data of the normalized difference vegetation index, environmental factors were considered in generating a probability map with the aid of logistic regression. A Bayesian maximum entropy model was employed to explore the spatial and temporal correlations of HPAI incidence. The results show that proximity to water bodies and national highways was statistically relevant to the occurrence of HPAI. Migratory birds, mainly waterfowl, were important infection sources in HPAI transmission. In addition, the HPAI outbreaks had high spatiotemporal autocorrelation. This epidemic spatial range fluctuated 45 km owing to different distribution patterns of cities and water bodies. Furthermore, two outbreaks were likely to occur with a period of 22 d. The potential risk of occurrence of HPAI in Mainland China for the period from January 23 to February 17, 2004 was simulated based on these findings, providing a useful meta-model framework for the application of environmental factors in the prediction of HPAI risk.

Simulation of the spread of infectious diseases in a geographical environment.

The study of mathematical models for the spread of infectious diseases is an important issue in epidemiology. Given the fact that most existing models cannot comprehensively depict heterogeneities (e.g., the population heterogeneity and the distribution heterogeneity) and complex contagion patterns (which are mostly caused by the human interaction induced by modern transportation) in the real world, a theoretical model of the spread of infectious diseases is proposed. It employs geo-entity based cellular automata to simulate the spread of infectious diseases in a geographical environment. In the model, physical geographical regions are defined as cells. The population within each cell is divided into three classes: Susceptible, Infective, and Recovered, which are further divided into some subclasses by states of individuals. The transition rules, which determine the changes of proportions of those subclasses and reciprocal transformation formulas among them, are provided. Through defining suitable spatial weighting functions, the model is applied to simulate the spread of the infectious diseases with not only local contagion but also global contagion. With some cases of simulation, it has been shown that the results are reasonably consistent with the spread of infectious diseases in the real world. The model is supposed to model dynamics of infectious diseases on complex networks, which is nearly impossible to be achieved with differential equations because of the complexity of the problem. The cases of simulation also demonstrate that efforts of all kinds of interventions can be visualized and explored, and then the model is able to provide decision-making support for prevention and control of infectious diseases.