Kawasaki disease (KD) is a systemic febrile, inflammatory vascular disease of unknown etiology. The coronary artery abnormality (CAA) caused by KD has become the most commonly acquired heart disease ...in children. Initial treatment of intravenous immunoglobulin (IVIG) can reduce the incidence of CAA. Thrombocytosis is common during the course of KD, but changes in and significances of platelet function and parameters are unclear. In this study, we enrolled 120 patients, including 40 patients with KD, 40 febrile controls, and 40 afebrile controls. The platelet function was assessed using the platelet function analyzer (PFA)-200. Platelet parameters, including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet hematocrit (PCT) were measured. In the febrile period, the PDW and MPV were lower in KD patients (P < 0.05). The platelet function did not change significantly during the febrile period of KD but weakened in the defervescence phase. No significant differences between the CAA and normal groups, and between IVIG resistance and response groups. The diagnostic cutoff value of the PDW level for predicting KD was 10.85 fL with a sensitivity of 55% and a specificity of 77.5% (area under curve (AUC) = 0.690, 95% confidence interval (CI): 0.574-0.806, P < 0.01). Besides, the MPV level was 9.55 fL with sensitivity of 75% and specificity of 70% (AUC = 0.733, 95%CI: 0.620-0.846, P < 0.001). This is the first longitudinal study of platelet function changes in KD patients using PFA-200. Besides, lower PDW and MPV may be available markers for early diagnosis of KD.
The average household size in China has declined over the past few decades and will continue to drop, which leads to a loss of scale economies. Its implications for electricity demand and ...sustainability could be especially profound because of the high ecological/environmental intensity of electricity in China and the expected boom in demand. Using nationally representative household survey panels from 2010 to 2016, we identified substantial household scale economies in electricity consumption. Specifically, reducing household size by one incurs a 17.0–23.6% increase in consumption. We further assessed the ecological/environmental implications in China. CO2 emission, water withdrawal, smoke ash emission, SO2 emission, NOx emission, and industrial wastewater discharge were found to increase with a smaller household size. For example, a household size reduction of 0.5 (to 2.5 members) by 2030–2035 could result in a 0.5% increase in CO2 emission and a 0.3% increase in water withdrawal as compared with the levels in 2015. The increase in CO2 emission is almost equal to the entire emissions of Portugal. It is therefore essential to incorporate scale effect into energy demand projections and sustainability assessments. The results also highlight the urgency in transitioning to cleaner energy since household size shrinkage is occurring globally.
•We used a household panel survey to explore electricity consumption in China.•We identified a significant economies of scale effect in household consumption.•Average household size is expected to continue declining in China.•Household size decline has profound sustainability implications.
Reporting on brucellosis, a relatively rare infectious disease caused by Brucella, is often delayed or incomplete in traditional disease surveillance systems in China. Internet search engine data ...related to brucellosis can provide an economical and efficient complement to a conventional surveillance system because people tend to seek brucellosis-related health information from Baidu, the largest search engine in China. In this study, brucellosis incidence data reported by the CDC of China and Baidu index data were gathered to evaluate the relationship between them. We applied an autoregressive integrated moving average (ARIMA) model and an ARIMA model with Baidu search index data as the external variable (ARIMAX) to predict the incidence of brucellosis. The two models based on brucellosis incidence data were then compared, and the ARIMAX model performed better in all the measurements we applied. Our results illustrate that Baidu index data can enhance the traditional surveillance system to monitor and predict brucellosis epidemics in China.
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•Symbiosis of microalgae-bacteria has been used to enhance tetracycline removal.•The highest removal percentage of TET reached 95% when the coculture ratio was 1:2.•The nutrient ...exchange relationship was studied and does not affect presence of TET.•Desmodesmus sp.: K. pneumoniae coculture would be a green approach to remove TET.
A sustainable approach of Desmodesmus sp. GIEC-179: Klebsiella pneumoniae (DUT-XJR-t-1.2) co-culture ratios were optimized to remove tetracycline (TET) from synthetic wastewater. To enhance the tetracycline removal performance, the effect of microalgae-bacterial co-culture ratio, maximum TET concentration, effective inoculum amount, growth temperature and pH were studied. The optimized ratio 1:2 of Desmodesmus sp.: K. pneumoniae showed the optimal removal percentage at the temperature of 25 °C, pH 7 and 10% inoculum amount; and the removal of TET was recorded as 95%. Moreover, this study explored the Desmodesmus sp.: K. pneumoniae (1:2) nutrient (COD, NH4+ and PO43−) exchange relationship and their interaction of TET removal to better understand their fundamental mechanism. According to the results of this study, Desmodesmus sp.: K. pneumoniae co-culture could be a green option for bio-removal of tetracycline from wastewater.
Sigma-1 receptor (Sig-1R) is a ligand-regulated endoplasmic reticulum (ER) chaperone involved in cardiac hypertrophy, but it is not known whether Sig-1R is regulated by microRNAs (miRNAs). According ...to bioinformatic analysis, miR-297 was suggested as a potential target miRNA for Sig-1R. Therefore, we verified whether miR-297 could target Sig-1R and investigated the possible mechanisms underlying the role of miR-297 in cardiac hypertrophy.
Bioinformatic analysis combined with laboratory experiments, including quantitative RT-PCR, Western blotting, and luciferase assay, were performed to identify the target miRNA of Sig-1R. Transverse aortic constriction (TAC) model and neonatal rat cardiomyocytes (NCMs) stimulated with angiotensin II (AngII) were used to explore the relationship between miR-297 and Sig-1R. Additionally, the function of miR-297 in cardiomyocyte hypertrophy and ER stress/unfolded protein response (UPR) signaling pathway was investigated by transfecting miR-297 mimics/inhibitor.
miR-297 levels were increased in both TAC-induced hypertrophic heart tissue and AngII-induced cardiomyocyte hypertrophy. Up-regulation of miR-297 by specific mimics exacerbated AngII-induced cardiomyocyte hypertrophy, whereas inhibition of miR-297 suppressed the process. During cardiomyocyte hypertrophy, Sig-1R expression, which was negatively regulated by miR-297 by directly targeting its 3′untranslated region (UTR), was decreased. Furthermore, attenuation of miR-297 inhibited the activation of X-box binding protein 1 (Xbp1) and activating transcriptional factor 4 (ATF4) signaling pathways in NCMs.
Our data demonstrate that miR-297 promotes cardiomyocyte hypertrophy by inhibiting the expression of Sig-1R and activation of ER stress signaling, which provides a novel interpretation for cardiac hypertrophy.
The annual globally averaged atmospheric carbon dioxide concentration is expected to reach 550 ppm around 2050 unless measures are taken to mitigate its increase. Field experiments suggest that the ...nutrient contents of food crops are decreased substantially under elevated carbon dioxide conditions, which will lead to additional nutritional consequences on top of those related to the expected reductions of crop yield. Global modeling studies have suggested that such impacts would lead to a marked increase in the prevalence of nutrient deficiency. By using individual-level dietary survey data for Chinese adults, we conducted a comprehensive analysis on the nutritional consequence under the 550-ppm carbon dioxide scenario, with paying special attention to the distributional impact of nutrition degradation on different income groups. Our results suggest that the Chinese adult population would ingest around 2.17–4.75% less protein, iron, and zinc, and consequently, the prevalence of nutrient deficiency would increase by 1.35–4.42%. We also found a significant disparity in the nutrient loss rate and risk of deficiency among income groups: nutrient loss rates for the lowest-income group were 1.37–1.54 times greater than those for the highest-income group. Thus, the lowest-income group would experience a more considerable increase of nutrient deficiency risk under the 550-ppm carbon dioxide scenario. Moreover, we found that in the lower-income group nutrient intake for all three nutrients would be reduced simultaneously, which would leave this population more vulnerable to nutritional health risks. Our study revealed a marked inequality in the impact of the elevation of atmospheric carbon dioxide concentration. Nutrition intervention policies explicitly targeting affected populations must be explored to achieve social equality under elevated atmospheric carbon dioxide concentrations.
Plant leaf 3D architecture changes during growth and shows sensitive response to environmental stresses. In recent years, acquisition and segmentation methods of leaf point cloud developed rapidly, ...but 3D modelling leaf point clouds has not gained much attention. In this study, a parametric surface modelling method was proposed for accurately fitting tea leaf point cloud. Firstly, principal component analysis was utilized to adjust posture and position of the point cloud. Then, the point cloud was sliced into multiple sections, and some sections were selected to generate a point set to be fitted (PSF). Finally, the PSF was fitted into non-uniform rational B-spline (NURBS) surface. Two methods were developed to generate the ordered PSF and the unordered PSF, respectively. The PSF was firstly fitted as B-spline surface and then was transformed to NURBS form by minimizing fitting error, which was solved by particle swarm optimization (PSO). The fitting error was specified as weighted sum of the root-mean-square error (RMSE) and the maximum value (MV) of Euclidean distances between fitted surface and a subset of the point cloud. The results showed that the proposed modelling method could be used even if the point cloud is largely simplified (RMSE < 1 mm, MV < 2 mm, without performing PSO). Future studies will model wider range of leaves as well as incomplete point cloud.
The glycocalyx is a complex polysaccharide-protein layer lining the lumen of vascular endothelial cells. Changes in the structure and function of the glycocalyx promote an inflammatory response in ...blood vessels and play an important role in the pathogenesis of many vascular diseases (e.g., diabetes, atherosclerosis, and sepsis). Vascular endothelial dysfunction is a hallmark of inflammation-related diseases. Endothelial dysfunction can lead to tissue swelling, chronic inflammation, and thrombosis. Therefore, elimination of endothelial inflammation could be a potential target for the treatment of vascular diseases. This review summarizes the key role of the glycocalyx in the inflammatory process and the possible mechanism by which it alleviates this process by interrupting the cycle of endothelial dysfunction and inflammation. Especially, we highlight the roles of different components of the glycocalyx in modulating the inflammatory process, including components that regulate leukocyte rolling, L-selectin binding, inflammasome activation and the signaling interactions between the glycocalyx components and the vascular cells. We discuss how the glycocalyx interferes with the development of inflammation and the importance of preventing glycocalyx impairment. Finally, drawing on current understanding of the role of the glycocalyx in inflammation, we consider a potential strategy for the treatment of vascular diseases.
OBJECTIVES/GOALS: To examine the prevalence of new indications for existing drugs conducted by non-originator companies from 2015 to 2021 and determine how many could qualify for 505(b)(2) under the ...Food, Drug, and Cosmetics Act. METHODS/STUDY POPULATION: A search within Clinicaltrials.gov was conducted to identify phase 3 drug interventional studies completed from 2015 to 2021. Results were categorized by funding source and industry sponsored studies were further separated into originator- and non-originator companies using dailymed.com. An in-depth review of 2018 was conducted to understand the nature of the studies including indication, dosage form, and route of administration. RESULTS/ANTICIPATED RESULTS: According to clinicaltrials.gov, a total of 7148 phase 3 studies were conducted between 2015 and 2021. Most of these studies were funded by industry (4447, 66.21%), followed by other (2428, 33.97%), NIH (266, 3.72%), and government (62, 0.87%). In-depth examination of the studies completed in 2018 (n=1077) revealed similar pattern in that most were funded by industry (674, 62.58%) followed by other (356, 33.05%), NIH (43, 3.99%), and government (10, 0.93%). Some studies were funded by more than one type. Of the industry-sponsored studies, 623 were funded by originator companies and 51 by non-originator companies. A total of 49/674 of the industry sponsored studies were for new indications, with 42 studies conducted by originator companies and 7 conducted by non-originator companies. DISCUSSION/SIGNIFICANCE: The 505(b)(2) is a way for manufacturers to add new indications to drugs by non-originator companies. In 2018, 49/674 studies were conducted to pursue new indications with few, 7/49, conducted by non-originator companies. The product development landscape reveals few opportunities for entities pursuing the 505(b)(2) pathway for new indications.
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