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Journal of Cellular and Molecular... Oct 2021Silicosis is an occupational disease characterized by extensive pulmonary fibrosis, and the underlying pathological process remains uncertain. Herein, we explored the...
Silicosis is an occupational disease characterized by extensive pulmonary fibrosis, and the underlying pathological process remains uncertain. Herein, we explored the molecular mechanism by which microRNA-205-5p (miR-205-5p) affects the autophagy of alveolar macrophages (AMs) and pulmonary fibrosis in mice with silicosis through the E2F transcription factor 1 (E2F1)/S-phase kinase-associated protein 2 (SKP2)/Beclin1 axis. Alveolar macrophages (MH-S cells) were exposed to crystalline silica (CS) to develop an in vitro model, and mice were treated with CS to establish an in vivo model. Decreased Beclin1 and increased SKP2 and E2F1 were identified in mice with silicosis. We silenced or overexpressed miR-205-5p, E2F1, SKP2 and Beclin1 to investigate their potential roles in pulmonary fibrosis in vivo and autophagy in vitro. Recombinant adenovirus mRFP-GFP-LC3 was transduced into the MH-S cells to assay autophagic flow. Knocking down Beclin1 promoted pulmonary fibrosis and suppressed the autophagy. Co-immunoprecipitation and ubiquitination assays suggested that SKP2 induced K48-linked ubiquitination of Beclin1. Furthermore, chromatin immunoprecipitation-PCR revealed the site where E2F1 bound to the SKP2 promoter between 1638 bp and 1645 bp. As shown by dual-luciferase reporter gene assay, the transfection with miR-205-5p mimic inhibited the luciferase activity of the wild-type E2F1 3'untranslated region, suggesting that miR-205-5p targeted E2F1. Additionally, miR-205-5p overexpression increased autophagy and reduced the pulmonary fibrosis, while overexpression of E2F1 or SKP2 or inhibition of Beclin1 could annul this effect. The current study elucidated that miR-205-5p targeted E2F1, thereby inhibiting SKP2-mediated Beclin1 ubiquitination to promote macrophage autophagy and inhibit pulmonary fibrosis in mice with silicosis.
Topics: Animals; Autophagy; Beclin-1; Cell Line; Databases, Genetic; Disease Models, Animal; E2F1 Transcription Factor; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunohistochemistry; Macrophages, Alveolar; Mice; MicroRNAs; Models, Biological; Promoter Regions, Genetic; Proteolysis; Pulmonary Fibrosis; S-Phase Kinase-Associated Proteins; Signal Transduction; Silicosis; Ubiquitination
PubMed: 34428336
DOI: 10.1111/jcmm.16825 -
PloS One 2021In sub-Saharan Africa growing season precipitation is affected by climate change. Due to this, in Cameroon, it is uncertain how some crops are vulnerable to growing...
In sub-Saharan Africa growing season precipitation is affected by climate change. Due to this, in Cameroon, it is uncertain how some crops are vulnerable to growing season precipitation. Here, an assessment of the vulnerability of maize, millet, and rice to growing season precipitation is carried out at a national scale and validated at four sub-national scales/sites. The data collected were historical yield, precipitation, and adaptive capacity data for the period 1961-2019 for the national scale analysis and 1991-2016 for the sub-national scale analysis. The crop yield data were collected for maize, millet, and rice from FAOSTAT and the global yield gap atlas to assess the sensitivity both nationally and sub-nationally. Historical data on mean crop growing season and mean annul precipitation were collected from a collaborative database of UNDP/Oxford University and the climate portal of the World Bank to assess the exposure both nationally and sub-nationally. To assess adaptive capacity, literacy, and poverty rate proxies for both the national and regional scales were collected from KNOEMA and the African Development Bank. These data were analyzed using a vulnerability index that is based on sensitivity, exposure, and adaptive capacity. The national scale results show that millet has the lowest vulnerability index while rice has the highest. An inverse relationship between vulnerability and adaptive capacity is observed. Rice has the lowest adaptive capacity and the highest vulnerability index. Sub-nationally, this work has shown that northern maize is the most vulnerable crop followed by western highland rice. This work underscores the fact that at different scales, crops are differentially vulnerable due to variations in precipitation, temperature, soils, access to farm inputs, exposure to crop pest and variations in literacy and poverty rates. Therefore, caution should be taken when transitioning from one scale to another to avoid generalization. Despite these differences, in the sub-national scale, western highland rice is observed as the second most vulnerable crop, an observation similar to the national scale observation.
Topics: Cameroon; Climate Change; Crop Production; Crops, Agricultural; Millets; Oryza; Rain; Seasons; Socioeconomic Factors; Zea mays
PubMed: 34106980
DOI: 10.1371/journal.pone.0252335 -
Materials Science & Engineering. C,... May 2021The recently proposed concept of quaternary bioreceptivity applies to substrates treated with coating materials and it is considered in the present study with the alga...
The recently proposed concept of quaternary bioreceptivity applies to substrates treated with coating materials and it is considered in the present study with the alga Bracteacoccus minor and the cyanobacterium Nostoc sp. onto granite specimens treated with ethyl silicate and nano-sized silica doped with different amounts of TiO (0, 0.5, 1 and 3 wt%). The findings showed a lack of correlation between the amount of TiO and the level of colonization (main bioreceptivity estimator) to the presence of cracks on the surface, which annul the biocidal power of TiO. Crack formation, which depends on the mechanical properties, greatly influences the bioreceptivity of the material. Thus, the cracks provided anchor points where water is retained, in turn strongly influencing the early stages of colonization kinetics, to a greater extent than the biocidal power of TiO, which will probably increase as the biofilm develops over the entire surface. In addition, although the cracks were more abundant and wider in the ethyl silicate-based consolidant, the nano-sized silica provided better anchoring points, making the material treated with the corresponding consolidant more bioreceptive.
Topics: Biofilms; Construction Materials; Ecosystem; Humans; Titanium
PubMed: 33947552
DOI: 10.1016/j.msec.2021.112058 -
Veterinary World Dec 2020Gentamicin (GM) is one of the most effective antibiotics for severe, life-threatening Gram-negative infections. Nevertheless, its clinical use has been restrained...
BACKGROUND AND AIM
Gentamicin (GM) is one of the most effective antibiotics for severe, life-threatening Gram-negative infections. Nevertheless, its clinical use has been restrained because of its nephrotoxic potential. Royal jelly (RJ) and aliskiren (ALK) can individually prevent such toxic effects. The aim of this study was to explore the protective effects of a combination treatment of RJ and ALK on GM-mediated nephrotoxicity.
MATERIALS AND METHODS
Thirty-two adult female. Wistar rats were divided equally into four groups: (I) Receiving normal saline; (II) GM (100 mg/kg, intraperitoneal [i.p.] injection); GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection); and (IV) GM (100 mg/kg, i.p. injection) plus ALK (50 mg/kg, i.p. injection) in combination with RJ (150 mg/kg, orally). All treatments were administered daily for 10 days. The blood levels of creatinine, urea, uric acid, albumin, and total protein were measured. Then, the animals were sacrificed, and the kidneys were taken for histopathology.
RESULTS
Compared to normal control rats, GM-injected rats showed significantly (p<0.001) higher serum concentrations of uric acid, urea, and creatinine as well as evidently (p<0.001) lower blood levels of albumin and total protein. Moreover, GM administration was associated with significant renal histopathological changes. All these alterations were considerably (p<0.05) improved in GM-injected rats receiving ALK compared to rats receiving GM alone. However, when RJ was given in combination with ALK to GM-injected rats, it lessened the beneficial nephroprotective effects of both agents.
CONCLUSION
The combination treatment of RJ and ALK is not desirable for GM-induced nephrotoxicity. Further studies are crucial to accurately explore the precise mechanism of RJ antagonistic interaction with ALK.
PubMed: 33487984
DOI: 10.14202/vetworld.2020.2658-2662 -
Frontiers in Bioengineering and... 2020Organ-on-chip (OOC) systems recapitulate key biological processes and responses exhibited by cells, tissues, and organs . Accordingly, these models of both health and... (Review)
Review
Organ-on-chip (OOC) systems recapitulate key biological processes and responses exhibited by cells, tissues, and organs . Accordingly, these models of both health and disease hold great promise for improving fundamental research, drug development, personalized medicine, and testing of pharmaceuticals, food substances, pollutants etc. Cells within the body are exposed to biomechanical stimuli, the nature of which is tissue specific and may change with disease or injury. These biomechanical stimuli regulate cell behavior and can amplify, annul, or even reverse the response to a given biochemical cue or drug candidate. As such, the application of an appropriate physiological or pathological biomechanical environment is essential for the successful recapitulation of behavior in OOC models. Here we review the current range of commercially available OOC platforms which incorporate active biomechanical stimulation. We highlight recent findings demonstrating the importance of including mechanical stimuli in models used for drug development and outline emerging factors which regulate the cellular response to the biomechanical environment. We explore the incorporation of mechanical stimuli in different organ models and identify areas where further research and development is required. Challenges associated with the integration of mechanics alongside other OOC requirements including scaling to increase throughput and diagnostic imaging are discussed. In summary, compelling evidence demonstrates that the incorporation of biomechanical stimuli in these OOC or microphysiological systems is key to fully replicating physiology in health and disease.
PubMed: 33363131
DOI: 10.3389/fbioe.2020.602646 -
Polymers Nov 2020The Arburg Plastic Freeforming process (APF) is a unique additive manufacturing material jetting method. In APF, a thermoplastic material is supplied as pellets, melted...
The Arburg Plastic Freeforming process (APF) is a unique additive manufacturing material jetting method. In APF, a thermoplastic material is supplied as pellets, melted and selectively deposited as droplets, enabling the use of commercial materials in their original shape instead of filaments. The medical industry could significantly benefit from the use of additive manufacturing for the onsite fabrication of customized medical aids and therapeutic devices in a fast and economical way. In the medical field, the utilized materials need to be certified for such applications and cannot be altered in any way to make them printable, because modifications annul the certification. Therefore, it is necessary to modify the processing conditions rather than the materials for successful printing. In this research, a medical-grade poly(methyl methacrylate) was analyzed. The deposition parameters were kept constant, while the drop aspect ratio, discharge rate, melt temperatures, and build chamber temperature were varied to obtain specimens with different geometrical accuracy. Once satisfactory geometrical accuracy was obtained, tensile properties of specimens printed individually or in batches of five were tested in two different orientations. It was found that parts printed individually with an XY orientation showed the highest tensile properties; however, there is still room for improvement by optimizing the processing conditions to maximize the mechanical strength of printed specimens.
PubMed: 33198390
DOI: 10.3390/polym12112677 -
International Journal For Equity in... Aug 2020Comprehensive primary care practices, through preconception, preventive, curative, and rehabilitative care, have been a global priority in the promotion of health....
BACKGROUND
Comprehensive primary care practices, through preconception, preventive, curative, and rehabilitative care, have been a global priority in the promotion of health. However, the scope of primary care services has still been in decline in China. Studies on the factors for primary care service scope have centred on human resources and infrastructure; the role of direct government subsidies (DGS) on services scope of primary care facilities were left unanswered. This study aimed to explore the association between the DGS and services scope of primary care facilities in China.
METHODS
A multi-stage, clustered cross-sectional survey using self-administrated questionnaire was conducted among primary care facilities of 36 districts/counties in China. A total of 770 primary care facilities were surveyed with 757 (98.3%) valid respondents. Of the 757 primary care facilities, 469 (62.0%) provided us detailed information of financial revenue and DGS from 2009 to 2016. Therefore, 469 primary care facilities from 31 counties/districts were included in this study. Sasabuchi-Lind-Mehlum tests and multivariate regression models were used to examine the inverted U-shaped relationship between the DGS and service scope.
RESULTS
Of 469 PCFs, 332 (70.8%) were township health centres. Proportion of annul DGS to FR arose from 26.5% in 2009 to 50.5% in 2016. At the low proportion of DGS to financial revenue, an increase in DGS was associated with an increased service scope of primary care facilities, whereas the proportion of DGS to financial revenue over 42.5% might cause narrowed service scope (P = 0.023, 95% CI 11.59-51.74%); for the basic medical care dimension, the cut point is 42.6%. However, association between DGS and service scope of public health by primary care facilities is statistically insignificant.
CONCLUSION
While the DGS successfully achieved equalization of basic preventive and public health services, the disproportionate proportion of DGS to financial revenue is associated with narrowed service scope, which might cause underutilization of primary care and distorted incentive structure of primary care. Future improvements of DGS should focus on the incentive of broader basic medical services provision, such as clarifying service scope of primary care facilities and strategic procurement with a performance-based subsidies system to determine resource allocation.
Topics: Ambulatory Care Facilities; China; Cross-Sectional Studies; Financing, Government; Health Facilities; Health Services; Humans; Primary Health Care; Public Health; Resource Allocation
PubMed: 32778111
DOI: 10.1186/s12939-020-01248-7 -
The Linacre Quarterly Nov 2019Questions of life and death are primarily philosophical questions, as philosopher Robert Spaemann argues. Spaemann argues that "brain death" is philosophically...
UNLABELLED
Questions of life and death are primarily philosophical questions, as philosopher Robert Spaemann argues. Spaemann argues that "brain death" is philosophically unsatisfactory as a definition of death, and as the exclusive criterion for determining death, for two main reasons: first, because it attempts to annul the basic perceptions of the ordinary person in regard to death. Second, because the cause of life and unity in a living being cannot be reduced to the brain. This essay is an explication of Spaemann's contribution to the "brain death" question, which consists in illuminating the philosophical issues at stake.
SUMMARY
This article presents Robert Spaemann's philosophical case that "brain death" suffices neither as a definition of death nor as the sole criterion of death.
PubMed: 32431430
DOI: 10.1177/0024363919876391 -
Optics Express Mar 2020In this study, the characterization of Hydrogen Chloride (HCl) seasonal variations and inter-annual linear trend are presented for the first time over the polluted...
In this study, the characterization of Hydrogen Chloride (HCl) seasonal variations and inter-annual linear trend are presented for the first time over the polluted region at Hefei (117°10'E, 31°54'N), China. The time series of HCl were retrieved by the mid-infrared (MIR) solar spectra recorded by the ground-based high-resolution Fourier transform infrared spectroscopy (FTIR) between July, 2015 and April, 2019. The magnitude of HCl reaches a peak in January (2.70 ± 0.16) × 10 molecules*cm and a minimum in September (2.27 ± 0.09) × 10 molecules*cm. The four-year time series of HCl total column show a negative linear trend of (-1.83 ± 0.13) %. The FTIR data are compared with GEOS-Chem data in order to evaluate the performance of the GEOS-Chem model to simulate HCl. In general, total column FTIR data and GEOS-Chem model data are in a good agreement with a correlation coefficient of 0.82. GEOS-Chem model data present a good agreement with FTIR data in seasonal variation and inter-annul trend. The maximum differences occur in January and April with mean differences of 4%-6%. We also present HCl time series observed by 6 NDACC stations (Bremen, Toronto, Rikubetsu, Izana, Reunion.maido, Lauder) in low-middle-latitude sites of the northern and southern hemispheres and Hefei stations in order to investigate the seasonal and annual trends of HCl in low-middle-latitude sites. The HCl total column at the northern hemisphere stations reached the maximum in the late winter or early spring and the minimum in the early winter or late autumn. In general, the seasonal variations of HCl over Hefei is similar to that in other northern hemisphere mid-latitude FTIR stations.
PubMed: 32225437
DOI: 10.1364/OE.384377 -
Scientific Reports Mar 2020Ecological degradation impedes sustainable development in Southwest China, and artificial afforestation has been a key strategy of the Government of China to effectively...
Ecological degradation impedes sustainable development in Southwest China, and artificial afforestation has been a key strategy of the Government of China to effectively curb it. However, the water consumed by large-scale afforestation has a huge impact on water supply in Southwest China, which also arise a new challenge causing severe drought here recently. In order to determine the impact of artificial afforestation on the region, this study conducts spatiotemporal, abrupt change, and correlation and regression analyses. Results show that although water resources fluctuate, they exhibit a general declining trend. Especially after 2000, water resources showed a significant downward trend. In terms of spatial tendency, there has been an obvious decrease in water resources in the Sichuan Basin, the mountainous region of eastern Chongqing, and the Yunnan-Guizhou Plateau. Due to extensive afforestation and vegetation cover growth, there has been an increase in most trends of forest-shrub ecosystems, resulting in substantially enhanced evapotranspiration effects. The uptake of water by afforestation in Southwest China could reach 40.42 billion m, which is equivalent to 10.69% of its annul available water supply (1980-2015). Generally, afforestation disrupts the water balance of the region. This study recommends substituting afforestation for natural restoration or, at the very least, selecting vegetation that requires less water for the restoration of the ecological environment of Southwest China, which provide scientific method for regional sustainable development.
PubMed: 32139773
DOI: 10.1038/s41598-020-61108-w