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Bioengineered Feb 2022Chronic heart failure (CHF) is a prevalent health concern with complex pathogenesis. This current study set out to estimate the function of the miR-129-5p/Smurf1/PTEN...
Chronic heart failure (CHF) is a prevalent health concern with complex pathogenesis. This current study set out to estimate the function of the miR-129-5p/Smurf1/PTEN axis on cardiac function injury in CHF. The model of CHF in rats was established. The cardiac function indexes, myocardial tissue damage, and oxidative stress-related factors in CHF rats were evaluated after the interference of Smurf1/miR-129-5p/PTEN. The targeting relationships between miR-129-5p and Smurf1 and between PTEN and Smurf1 were verified. It was found that that after modeling, cardiac functions were impaired, heart/left ventricular/lung weight and the myocardial structure was destroyed, and the degree of fibrosis of myocardial tissue was increased. After Smurf1 knockdown, the cardiac function, myocardial structure, and oxidative stress were improved, and the fibrosis in myocardial tissue was decreased. Smurf1 was a target of miR-129-5p. miR-129-5p could annul the protective effect of Smurf1 silencing on CHF rats. Smurf1 inhibited PTEN expression by promoting PTEN ubiquitination, while miR-129-5p enhanced PTEN expression by inhibiting Smurf1. Meanwhile, overexpression of PTEN annulled the cardiac dysfunction in CHF rats induced by Smurf1. In conclusion, miR-129-5p targeted Smurf1 and repressed the ubiquitination of PTEN, and promoted PTEN expression, thus improving the cardiac function of CHF rats.
Topics: Animals; Chronic Disease; Gene Expression Regulation, Enzymologic; Heart Failure; Male; MicroRNAs; PTEN Phosphohydrolase; Rats; Rats, Wistar; Ubiquitin-Protein Ligases
PubMed: 35034538
DOI: 10.1080/21655979.2021.2024335 -
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 -
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 -
Journal of Applied Behavior Analysis Jun 2021Despite the utility of experimental functional analysis methodology, not all applications produce differentiated results. Factors such as interaction effects or...
Despite the utility of experimental functional analysis methodology, not all applications produce differentiated results. Factors such as interaction effects or methodological inefficiencies may compromise the likelihood of obtaining differentiated outcomes. Various studies have addressed methods to improve the efficiency of experimental functional analysis methodology (e.g., analysis of within-session responding). In the current study, we describe an updated model for progressing from brief to extended experimental analyses. The model incorporates several procedural refinements developed over the past 20+ years of experimental functional analysis research and additional conditions to confirm or annul findings. We present data for 20 participants who were referred for assessment and treatment of a variety of behavior problems (e.g., stereotypy, aggression, self-injury). We generally terminated the analyses when response patterns were consistent with established best-practice functional analysis methodology. Results showed conclusive interpretations were obtained for 100% of participants.
Topics: Aggression; Humans; Problem Behavior; Reinforcement, Psychology; Self-Injurious Behavior; Stereotyped Behavior
PubMed: 33914341
DOI: 10.1002/jaba.841 -
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 -
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 -
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 -
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 -
Pathology International Aug 2019Humoral factors from cancer-associated fibroblasts (CAFs) reportedly affect epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance in cancer...
Secretion of high amounts of hepatocyte growth factor is a characteristic feature of cancer-associated fibroblasts with EGFR-TKI resistance-promoting phenotype: A study of 18 cases of cancer-associated fibroblasts.
Humoral factors from cancer-associated fibroblasts (CAFs) reportedly affect epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance in cancer cells with EGFR mutations. The aim of this study was to identify the robust humoral factors secreted from CAFs that induce the primary resistance to EGFR-TKI. We evaluated the EGFR-TKI sensitivity of EGFR-mutant lung adenocarcinoma cell line (PC-9) treated with condition media (CM) from 18 cases of CAFs and matched non-cancerous-tissue-associated fibroblasts (NCAFs). We measured the expression levels of hepatocyte growth factor (HGF), interleukin-6, fibroblast growth factor-2, insulin-like growth factor-1, and vascular endothelial growth factor-A in CAFs and NCAFs. We examined whether HGF neutralizing antibody could annul the EGFR-TKI resistance induced by CM from CAFs. Compared to CM from NCAFs, CM from CAFs increased the resistance of PC-9 cells to EGFR-TKI in five out of 18 cases. Relative expression ratio of HGF messenger RNA was significantly higher in these five CAFs compared to others (P = 0.0013), whereas other cytokines were not. In four of these five cases, the addition of HGF neutralizing antibody significantly decreased the survival ratio of PC-9 cells. This study suggests that the secretion of higher amounts of HGF is the robust feature of EGFR-TKI resistance-promoting CAFs.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Cancer-Associated Fibroblasts; Cell Line, Tumor; Cell Survival; Drug Resistance, Neoplasm; ErbB Receptors; Female; Hepatocyte Growth Factor; Humans; Lung Neoplasms; Male; Middle Aged; Phenotype; Protein Kinase Inhibitors
PubMed: 31339210
DOI: 10.1111/pin.12838 -
Risk Analysis : An Official Publication... Oct 2020Operational risk management of autonomous vehicles in extreme environments is heavily dependent on expert judgments and, in particular, judgments of the likelihood that...
Operational risk management of autonomous vehicles in extreme environments is heavily dependent on expert judgments and, in particular, judgments of the likelihood that a failure mitigation action, via correction and prevention, will annul the consequences of a specific fault. However, extant research has not examined the reliability of experts in estimating the probability of failure mitigation. For systems operations in extreme environments, the probability of failure mitigation is taken as a proxy of the probability of a fault not reoccurring. Using a priori expert judgments for an autonomous underwater vehicle mission in the Arctic and a posteriori mission field data, we subsequently developed a generalized linear model that enabled us to investigate this relationship. We found that the probability of failure mitigation alone cannot be used as a proxy for the probability of fault not reoccurring. We conclude that it is also essential to include the effort to implement the failure mitigation when estimating the probability of fault not reoccurring. The effort is the time taken by a person (measured in person-months) to execute the task required to implement the fault correction action. We show that once a modicum of operational data is obtained, it is possible to define a generalized linear logistic model to estimate the probability a fault not reoccurring. We discuss how our findings are important to all autonomous vehicle operations and how similar operations can benefit from revising expert judgments of risk mitigation to take account of the effort required to reduce key risks.
PubMed: 32562315
DOI: 10.1111/risa.13539