Members of the family Filoviridae, including Ebola virus (EBOV) and Marburg virus (MARV), cause severe hemorrhagic fever in humans and nonhuman primates. Given their high lethality, a comprehensive understanding of filoviral pathogenesis is urgently needed. In the present studies, we revealed that the exchange protein directly activated by cAMP 1 (EPAC1) gene deletion protects vasculature in ex vivo explants from EBOV infection. Importantly, pharmacological inhibition of EPAC1 using EPAC-specific inhibitors (ESIs) mimicked the EPAC1 knockout phenotype in the ex vivo model. ESI treatment dramatically decreased EBOV infectivity in both ex vivo vasculature and in vitro vascular endothelial cells (ECs). Furthermore, postexposure protection of ECs against EBOV infection was conferred using ESIs. Protective efficacy of ESIs in ECs was observed also in MARV infection. Additional studies using a vesicular stomatitis virus pseudotype that expresses EBOV glycoprotein (EGP-VSV) confirmed that ESIs reduced infection in ECs. Ultrastructural studies suggested that ESIs blocked EGP-VSV internalization via inhibition of macropinocytosis. The inactivation of EPAC1 affects the early stage of viral entry after viral binding to the cell surface, but before early endosome formation, in a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-dependent manner. Our study delineated a new critical role of EPAC1 during EBOV uptake into ECs.

Binderless zeolite macrostructures in the form of ZK-4 microspheres were prepared using anion-exchange resin beads as shape-directing macrotemplates. The particles were synthesized under hydrothermal conditions at different temperatures and treatment times. The influence of the different synthesis parameters was investigated by X-ray diffraction, scanning electron microscopy, fluorescence X, nitrogen adsorption measurements and 29Si solid-state NMR. Fully crystalline spheres similar in size and shape to the original resin beads were obtained by a hydrothermal treatment at the highest temperatures (150⁻180 °C) for a short treatment time of 24 h. The synthesized microspheres showed to be promising in the molecular decontamination of volatile organic compounds (VOCs).

Urinary tract obstruction and the subsequent development of hydronephrosis can cause kidney injuries, which results in chronic kidney disease. Although it is important to detect kidney injuries at an early stage, new biomarkers of hydronephrosis have not been identified. In this study, we examined whether vanin-1 could be a potential biomarker for hydronephrosis. Male Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO). On day 7 after UUO, when the histopathological renal tubular injuries became obvious, the vanin-1 level in the renal pelvic urine was significantly higher than that in voided urine from sham-operated rats. Furthermore, vanin-1 remained at the same level until day 14. There was no significant difference in the serum vanin-1 level between sham-operated rats and rats with UUO. In the kidney tissue, the mRNA and protein expressions of vanin-1 significantly decreased, whereas there was increased expression of transforming growth factor (TGF)-β1 and Snail-1, which plays a pivotal role in the pathogenesis of renal fibrosis via epithelial-to-mesenchymal transition (EMT). These results suggest that vanin-1 in the renal pelvic urine is released from the renal tubular cells of UUO rats and reflects renal tubular injuries at an early stage. Urinary vanin-1 may serve as a candidate biomarker of renal tubular injury due to hydronephrosis.

Ciprofloxacin (CIP) is a potent antimicrobial agent with multiple effects on host cells and tissues. Previous studies have highlighted their proapoptotic effect on human cancer cells. The current study showed that subtoxic doses of CIP effectively sensitized multiple cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Although TRAIL alone mediated the partial proteolytic processing of procaspase-3 in lung cancer cells, co-treatment with CIP and TRAIL efficiently restored the complete activation of caspases. We found that treatment of lung cancer with CIP significantly upregulated the expression and protein stability of death receptor (DR) 5. These effects were mediated through the regulation of transcription factor CCAT enhancer-binding protein homologous protein (CHOP) since the silencing of these signaling molecules abrogated the effect of CIP. Taken together, these results indicated that the upregulation of death receptor expression and protein stability by CIP contributed to the restoration of TRAIL-sensitivity in lung cancer cells.

The impact of exposure to lead on child neurodevelopment has been well established. However, sex differences in vulnerability are still not fully explained. We aimed at evaluating the effect of a low-level lead exposure, as measured between 20 to 24 weeks of pregnancy and in cord blood, on developmental scores up to 24 months of age in 402 children from the Polish Mother and Child Cohort (REPRO_PL). Additionally, sex-dependent susceptibility to lead at this very early stage of psychomotor development was assessed. The blood lead levels were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). In order to estimate the children's neurodevelopment, the Bayley Scales of Infant and Toddler Development was applied. The geometric mean (GM) for blood lead level during 20⁻24 weeks of pregnancy was 0.99 ± 0.15 µg/dL and, in the cord blood, it was 0.96 ± 0.16 µg/dL. There was no statistically significant impact of lead exposure during prenatal period on the girls' psychomotor abilities. Among the boys, we observed lower scores for cognitive functions, along with increasing cord blood lead levels (β = -2.07; p = 0.04), whereas the results for the language and motor abilities were not statistically significant (p > 0.05). Our findings show that fetal exposure to very low lead levels might affect early cognitive domain, with boys being more susceptible than girls. Education on health, higher public awareness, as well as intervention programs, along with relevant regulations, are still needed to reduce risks for the vulnerable population subgroups.

Flower of Abelmoschus manihot (FAM) is clinically effective to treat chronic kidney disease (CKD) with a relatively high dosage. To improve the efficacy and the compliance of patients, macroporous resins were adopted to enrich and purify flavonoids from FAM, which are thought to be the major renal protective constituents in FAM. After screening six different kinds of macroporous resins, HPD-100 was selected for its great adsorption and desorption capacity. Then, orthogonal design tests were used to optimize parameters in the processes of impurity removal and flavonoids of FAM desorption on column chromatogram. Moreover, process scale-up was performed, and purification effects maintained after amplification. After purification, the content of seven main flavonoids in the product increased from 8.29% to 51.43%. Protective and anti-inflammatory effects of crude extract and the flavonoid component of FAM after purification were investigated on the adriamycin-damaged HK-2 cells and lipopolysaccharide-stimulated Raw 264.7 cells models. Both bioactivities were improved greatly after purification for these two cell models. Therefore, the purification process had enriched the main bioactive constituents with potential alleviating kidney injury activities. The flavonoid component of FAM is worthy of being developed as an improved remedy for CKD with better patients' compliance.

Kraft lignin was catalytically graphitized to graphene-based nanostructures at 1000 °C under argon atmosphere with four iron catalysts, iron(III) nitrate (Fe-N); iron(II) chloride (Fe-Cl₂); iron(III) chloride (Fe-Cl₃); and iron(II) sulfate (Fe-S). The catalytic decomposition process of iron-promoted lignin materials was examined using thermalgravimetric analysis and temperature-programmed decomposition methods. The crystal structure, morphology and surface area of produced materials were characterized by means of X-ray diffraction, Raman, scanning electron microscopy, high resolution transmission electron microscopy and N₂ adsorption-desorption techniques. Experimental results indicated that iron nitrate catalyst had better iron dispersion three other iron salts. Iron nitrate was the most active catalyst among four iron salts. The low activity of iron in iron chloride-promoted samples was because the residual chlorine over iron surfaces prevent iron interaction with lignin functional groups.

Background: The purpose of this study was to examine the convergent validity of the Polar Active Watch (PAW), a consumer-grade wrist-worn activity monitor, against waist- and wrist-worn research-grade monitors, the ActiGraph GT3X+/GT9X accelerometers, in children. Methods: Fifty-one children (18 boys; mean age = 10.30 ± 0.91 years) wore the three monitors (PAW, GT3X+, and GT9X) during an 80-min afterschool program across five school days. Time spent in sedentary, light-intensity (LPA), and moderate- and vigorous-intensity physical activity (MVPA) were estimated from each monitor. The correlation, mixed model, mean absolute percentage error, equivalence testing, and Bland-Altman analyses were used to examine the comparability of PA estimates of the PAW with GT3X+/GT9X accelerometers. Results: Moderate to strong correlations for sedentary and MVPA minutes, and weak correlation for LPA were observed between the PAW and GT3X+/GT9X accelerometers. Significant mean differences were found, where the PAW tended to overestimate time in sedentary and MVPA and underestimate LPA minutes, compared to the GT3X+/GT9X accelerometers. However, a non-significant mean difference in MVPA minutes was observed when using an adjusted MET threshold (≥4 METs) for the PAW, compared to the GT3X+ accelerometer. Conclusions: The PAW showed moderate convergent validity for sedentary and MVPA minutes against the GT3X+/GT9X accelerometers. However, caution is needed in the direct comparison between the monitors due to relatively large mean differences and within-group variability.

In the present study, the newly synthesized castor oil-derived thioether-containing ω-hydroxyacid (TEHA) block copolymers with polycaprolactone (TEHA-b-PCL), with methoxypoly(ethylene glycol) (mPEG), (TEHA-b-mPEG) and with poly(ethylene glycol) (PEG) (TEHA-b-PEG-b-TEHA), were investigated as polymeric carriers for fabrication of naltrexone (NLX)-loaded microspheres by the single emulsion solvent evaporation technique. These microspheres are appropriate for the long-term treatment of opioid/alcohol dependence. Physical properties of the obtained microspheres were characterized in terms of size, morphology, drug loading capacity, and drug release. A scanning electron microscopy study revealed that the desired NLX-loaded uniform microspheres with a mean particle size of 5⁻10 µm were obtained in all cases. The maximum percentage encapsulation efficiency was found to be about 25.9% for the microspheres obtained from the TEHA-b-PEG-b-TEHA copolymer. Differential scanning calorimetry and X-ray diffractometry analysis confirmed the drug entrapment within microspheres in the amorphous state. In vitro dissolution studies revealed that all NLX-loaded formulations had a similar drug release profile: An initial burst release after 24 h, followed by a sustained and slower drug release for up to 50 days. The analysis of the release kinetic data, which were fitted into the Korsmeyer⁻Peppas release model, indicated that diffusion is the main release mechanism of NLX from TEHA-b-PCL and TEHA-b-mPEG microspheres, while microspheres obtained from TEHA-b-PEG-b-TEHA exhibited a drug release closer to an erosion process.

Entamoeba histolytica is an invasive, pathogenic parasite causing amoebiasis. Given that proteins involved in transmembrane (TM) transport are crucial for the adherence, invasion, and nutrition of the parasite, we conducted a genome-wide bioinformatics analysis of encoding proteins to functionally classify and characterize all the TM proteins in E. histolytica. In the present study, 692 TM proteins have been identified, of which 546 are TM transporters. For the first time, we report a set of 141 uncharacterized proteins predicted as TM transporters. The percentage of TM proteins was found to be lower in comparison to the free-living eukaryotes, due to the extracellular nature and functional diversification of the TM proteins. The number of multi-pass proteins is larger than the single-pass proteins; though both have their own significance in parasitism, multi-pass proteins are more extensively required as these are involved in acquiring nutrition and for ion transport, while single-pass proteins are only required at the time of inciting infection. Overall, this intestinal parasite implements multiple mechanisms for establishing infection, obtaining nutrition, and adapting itself to the new host environment. A classification of the repertoire of TM transporters in the present study augments several hints on potential methods of targeting the parasite for therapeutic benefits.

2,3-O-acetylated-1,4-β-d-glucomannan (DOP-1-1) is a polysaccharide isolated from the stem of Dendrobium officinale. DOP-1-1 has been demonstrated to have remarkable immunomodulatory properties, but little is known about the influence of its structural diversity on bioactivity (and even less about the exact mechanism underlying its immune responses). First, DOP-1-1 was stabilized at different temperatures and pH conditions based on differential scanning calorimetry and size exclusion-chromatography⁻high-performance liquid chromatography. Then, a detailed study on the effects of DOP-1-1 on a human leukemia monocytic cell line (THP-1) under normal conditions was undertaken. DOP-1-1 promoted the translocation of nuclear factor-kappa B (NF-κB) and degradation of IκB proteins. The expression of genes and proteins closely associated with the immune, survival and apoptotic functions of NF-κB were analyzed by quantitative real-time RT-PCR. Furthermore, CCL4 and IP10 were confirmed to be the novel targets of the immune response stimulated by DOP-1-1. The phosphorylation of NF-кB was inhibited by treatment with a toll-like receptor 4 (TLR4) antagonist (TAK-242) and myeloid differentiation factor 88 (MyD88) inhibitor (ST2825). These data suggested: (i) the O-acetylated glucomannan DOP-1-1 is present in the steady state in low-pH solutions; (ii) DOP-1-1 can induce an immune response through NF-кB mediated by a TLR4 signaling pathway; and (iii) CCL4 and IP10 could be the novel targets of the immune response stimulated by O-acetylated glucomannan.

The aging population is a big challenge all over the world. However, there are few studies to date investigating the effects of trace element and mineral levels in drinking water and soil (especially in karst areas) on longevity. This study aims to examine temporal and spatial variations in longevity in Hechi (which is recognized as a longevity city) and to investigate relationships between longevity and trace element and mineral levels in drinking water and soils in this city (the karst landscape). Population data were collected from relevant literature and four national population censuses in 1982, 1990, 2000 and 2010. Drinking water and soil samples from Hechi were collected and analyzed. The results demonstrated an obvious clustered distribution for the longevity population in Hechi that has existed stably for decades. The longevity index tended to be significantly positively correlated with H₂SiO₃, Ca and Fe in drinking water and significantly negatively correlated with Sr in soil, indicating that drinking water characteristics contributed significantly to the observed regional longevity. The karst landscape is responsible for abundant trace elements in underground rivers in Hechi, which are beneficial to human health when consumed as drinking water. Good quality and slightly alkaline drinking water rich in trace elements such as H₂SiO₃, Ca, Fe, Na, Mg and low in heavy metals such as Pb and Cd might be an important factor contributing to the longevity phenomenon in Hechi.

In practice, it remains unclear what the best dietary approach is in subjects with pollen-related food allergy (PRFA). Our objective was to evaluate the effect of (1) dietary avoidance advice, (2) oral immunotherapy (OIT), (3) (heat) processing, and (4) consumption of hypoallergenic cultivars on frequency, severity, and eliciting dose of pollen-related food allergic reactions. A systematic search was conducted in PubMed, Embase, and Cochrane. All studies performing an in vivo investigation of one of the four interventions in adults with PRFA were included. Each study was assessed for quality and validity. Available data on frequency, severity, and eliciting dose of allergic reactions were extracted. Ten studies matched the eligibility criteria. No studies were retrieved on dietary avoidance advice. Two studies (N = 92) on apple OIT reported that tolerance was induced in 63% and 81% of subjects. Four studies (total N = 116) focused on heat processing. Heating was found to completely eradicate symptoms in 15⁻71% of hazelnut allergic and 46% of celery allergic individuals. Four studies (N = 60) comparing low to high allergenic apple cultivars revealed that Santana (and possibly Elise) apples seemed to cause milder reactions than Golden Delicious. In the awareness that overall level of evidence was low, we conclude that OIT, heat processing, and hypoallergenic cultivars may diminish or completely prevent allergic reactions in some but not all subjects with PRFA.

With regional socio-economic development and increasing population, the structure and function of terrestrial ecosystem environments on the earth's surface have changed markedly. Ecological shelter zone reconstruction (ESZR) is an ecosystem restoration and conservation project, which aims to ensure the safety of the ecological environments of-regions and basins. We selected the upper reaches of the Yangtze River (from Yibin to Chongqing) as the study area and determined the connotation of ESZR. At the same time, the planning scope and construction content of the ecological barrier in this specific region have been preliminarily explored. Meanwhile, a set of related planning methods was proposed, the ecological effects of which were quantitatively assessed and confirmed through the calculation of ESVs. Compared with the conditions in 2005, the study showed that the value of the services of the whole ecosystem augmented significantly under the slope classification, increasing by 103.23%. At the same time, the land use pattern has been optimized, and the vegetation coverage has been enhanced. The ESZR can effectively improve the ecosystem service function of slope land (mainly slope > 25°) and the regional ecological environment, solve the rocky desertification of the study area and provide an effective decision in relation to supporting regional green sustainable development.

Presently, natural sources and herbs are being sought for the treatment of human oral squamous cell carcinoma (OSCC) in order to alleviate the side effects of chemotherapy. This study investigates the effect of sandensolide, a cembrane isolated from Sinularia flexibilis, to inhibit human OSCC cell growth with the aim of developing a new drug for the treatment of oral cancer. In vitro cultured human OSCC models (Ca9.22, SCC9 and HSC-3 cell lines) and oral normal cells (HGF-1), as well as a zebrafish xenograft model, were used to test the cytotoxicity of sandensolide (MTT assay), as well as to perform cell cycle analysis and Western blotting. Both the in vitro bioassay and the zebrafish xenograft model demonstrated the anti-oral cancer effect of sandensolide. Moreover, sandensolide was able to significantly suppress colony formation and induce apoptosis, as well as cell cycle arrest, in OSCC by regulating multiple key proteins. Induction of reactive oxygen species (ROS) was observed in sandensolide-treated oral cancer cells. However, these apoptotic changes were rescued by NAC pretreatment. These findings contribute to the knowledge of the model of action of sandensolide, which may induce oxidative stress-mediated cell death pathways as a potential agent in oral cancer therapeutics.

Image matching is an outstanding issue because of the existing of geometric and radiometric distortion in stereo remote sensing images. Weighted α-shape (WαSH) local invariant features are tolerant to image rotation, scale change, affine deformation, illumination change, and blurring. However, since the number of WαSH features is small, it is difficult to get enough matches to estimate the satisfactory homography matrix or fundamental matrix. In addition, the WαSH detector is extremely sensitive to image noise because it is built on sampled edges. Considering the shortcomings of the WαSH detector, this paper improves the WαSH feature matching method based on the 2D discrete wavelet transform (2D-DWT). The method firstly performs 2D-DWT on the image, and then detects WαSH features on the transformed images. According to the methods of descriptor construction for WαSH features, three matching methods on the basis of wavelet transform WαSH features (WWF), improved wavelet transform WαSH features (IWWF), and layered IWWF (LIWWF) are distinguished with respect to the character of the sub-images. The experimental results on the dataset containing affine distortion, scale distortion, illumination change, and noise images, showed that the proposed methods acquired more matches and better stableness than WαSH. Experimentation on remote sensing images with less affine distortion and slight noise showed that the proposed methods obtained the correct matching rate greater than 90%. For images containing severe distortion, KAZE obtained a 35.71% correct matching rate, which is unacceptable for calculating the homography matrix, while IWWF achieved a 71.42% correct matching rate. IWWF was the only method that achieved the correct matching rate of no less than 50% for all four test stereo remote sensing image pairs and was the most stable compared to MSER, DWT-MSER, WαSH, DWT-WαSH, KAZE, WWF, and LIWWF.

WRKY transcription factors, so named because of the WRKYGQK heptapeptide at the N-terminal end, are widely distributed in plants and play an important role in physiological changes and response to biotic and abiotic stressors. Many previous studies have focused on the evolution of WRKY transcription factors in a given plant; however, little is known about WRKY evolution in legumes. The gene expression pattern of duplicated WRKY transcription factors remains unclear.

Evidence suggests that daily supplementation of 1500 to 2000 mg of calcium during pregnancy reduces pregnancy-induced hypertension (PIH). However, the evidence on the efficacy of low-dose calcium supplementation on PIH is limited. This paper assesses the longitudinal correlation between low-dose calcium intake (500 mg daily) and change in blood pressure during pregnancy among a homogeneous population in terms of hypertension and pre-eclampsia.

DNA methylation (DNAm) age was found to be an indicator for all-cause mortality, cancer incidence, and longevity, but no study has involved in the associations of DNAm age with the prognosis of breast cancer.

More patients are dying in non-palliative care settings than in palliative care settings. How health care providers care for adult patients at the end-of-life stage in non-palliative care settings has not been adequately explored. The aim of this study was to explore the experiences of health care providers in caring for patients at the end-of-life stage in non-palliative care settings.