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Osteoarthritis (OA) is a considerable health problem worldwide, and the prevalence of OA varies in different regions. In this study, the prevalence of OA in Kashin-Beck disease (KBD) and non-KBD endemic areas was examined, respectively. According to monitoring data, 4 types of regions (including none, mild, moderate and high KBD endemic areas) in Heilongjiang and Jilin provinces were selected. All local residents were eligible for inclusion criteria have undergone X-ray images of hands and anteroposterior image of knees. A total of 1673 cases were collected, 1446 cases were analyzed after removing the KBD patients (227). The overall hand OA and knee OA detection rates were 33.3% (481/1446) and 56.6% (818/1446), respectively. After being standardized by age, the detection rate of hand OA in the KBD endemic areas was significantly higher than that in the non-endemic endemic areas. Differently, there was no significant difference in the detection rates of knee OA between the KBD endemic areas and the non-endemic area. The correlation coefficient between the severity of OA and the severity of knee OA was 0.358 and 0.197 in the KBD and non-KBD endemic areas, respectively. Where the KBD historical prevalence level was higher, the severity of the residents' hand OA was more serious. The detection rates of hand OA and knee OA increased with age. The detection rate of knee OA increased with the increase in body mass index. The prevalence of hand OA was closely related to the pathogenic factors of Kashin-Beck disease, and the prevalence of knee OA had no significant correlation with KBD pathogenic factors.

Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied. In this study, we investigated the effects of Rev-D4F on peripheral blood cell subpopulations in C57 mice treated with a high fat diet and the mechanism of Rev-D4F in improving the function of EPCs impaired by tumor necrosis factor-α (TNF-α). The high fat diet significantly decreased the number of EPCs, EPC migratory functions, and the percentage of lymphocytes in the white blood cells. However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma. Rev-D4F clearly inhibited the effect of the high fat diet on the quantification of peripheral blood cell subpopulations and cytokine levels, and increased stromal cell derived factor 1α (SDF-1α) in the plasma. We provided in vitro evidence that TNF-α impaired EPC proliferation, migration, and tube formation through inactive AKT and eNOS, which was restored by Rev-D4F treatment. In contrast, both the PI3-kinase (PI3K) inhibitor (LY294002) and AKT inhibitor (perifosine) obviously inhibited the restoration of Rev-4F on EPCs impaired by TNF-α. Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

Lung cancer is one of the most common types of cancer and causes 1.38 million deaths annually, as of 2008 worldwide. Identifying natural anti-lung cancer agents has become very important. Gambogenic acid (GNA) is one of the active compounds of Gamboge, a traditional medicine that was used as a drastic purgative, emetic, or vermifuge for treating tapeworm. Recently, increasing evidence has indicated that GNA exerts promising anti-tumor effects; however, the underlying mechanism remains unclear. In the present paper, we found that GNA could induce the formation of vacuoles, which was linked with autophagy in A549 and HeLa cells. Further studies revealed that GNA triggers the initiation of autophagy based on the results of MDC staining, AO staining, accumulation of LC3 II, activation of Beclin 1 and phosphorylation of P70S6K. However, degradation of p62 was disrupted and free GFP could not be released in GNA treated cells, which indicated a block in the autophagy flux. Further studies demonstrated that GNA blocks the fusion between autophagosomes and lysosomes by inhibiting acidification in lysosomes. This dysfunctional autophagy plays a pro-death role in GNA-treated cells by activating p53, Bax and cleaved caspase-3 while decreasing Bcl-2. Beclin 1 knockdown greatly decreased GNA-induced cell death and the effects on p53, Bax, cleaved caspase-3 and Bcl-2. Similar results were obtained using a xenograft model. Our findings show, for the first time, that GNA can cause aberrant autophagy to induce cell death and may suggest the potential application of GNA as a tool or viable drug in anticancer therapies.

Mycoplasma hyopneumoniae is considered the major causative agent of porcine respiratory disease complex, occurs worldwide and causes major economic losses to the pig industry. To gain more insights into the pathogenesis of this organism, the high throughput cDNA microarray assays were employed to evaluate host responses of porcine alveolar macrophages to M. hyopneumoniae infection. A total of 1033 and 1235 differentially expressed genes were identified in porcine alveolar macrophages in responses to exposure to M. hyopneumoniae at 6 and 15 hours post infection, respectively. The differentially expressed genes were involved in many vital functional classes, including inflammatory response, immune response, apoptosis, cell adhesion, defense response, signal transduction, protein folding, protein ubiquitination and so on. The pathway analysis demonstrated that the most significant pathways were the chemokine signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway, nucleotide-binding oligomerization domains (Nod)-like receptor signaling pathway and apoptosis signaling pathway. The reliability of the data obtained from the microarray was verified by performing quantitative real-time PCR. The expression kinetics of chemokines was further analyzed. The present study is the first to document the response of porcine alveolar macrophages to M. hyopneumoniae infection. The data further developed our understanding of the molecular pathogenesis of M. hyopneumoniae.

Abnormal speech prosody has been widely reported in individuals with autism. Many studies on children and adults with autism spectrum disorder speaking a non-tonal language showed deficits in using prosodic cues to mark focus. However, focus marking by autistic children speaking a tonal language is rarely examined. Cantonese-speaking children may face additional difficulties because tonal languages require them to use prosodic cues to achieve multiple functions simultaneously such as lexical contrasting and focus marking. This study bridges this research gap by acoustically evaluating the use of Cantonese speech prosody to mark information structure by Cantonese-speaking children with and without autism spectrum disorder. We designed speech production tasks to elicit natural broad and narrow focus production among these children in sentences with different tone combinations. Acoustic correlates of prosodic focus marking like f0, duration and intensity of each syllable were analyzed to examine the effect of participant group, focus condition and lexical tones. Our results showed differences in focus marking patterns between Cantonese-speaking children with and without autism spectrum disorder. The autistic children not only showed insufficient on-focus expansion in terms of f0 range and duration when marking focus, but also produced less distinctive tone shapes in general. There was no evidence that the prosodic complexity (i.e. sentences with single tones or combinations of tones) significantly affected focus marking in these autistic children and their typically-developing (TD) peers. [ABSTRACT FROM AUTHOR]

Based on the background of urbanization in China, we used the dynamic spatial panel Durbin model to study the driving mechanism of ozone pollution empirically. We also analyzed the spatial distribution of ozone driving factors using the GTWR. The results show that: i) The average annual increase of ozone concentration in ambient air in China from 2015 to 2019 was 1.68μg/m3, and 8.39μg/m3 elevated the year 2019 compared with 2015. ii) The Moran's I value of ozone in ambient air was 0.027 in 2015 and 0.209 in 2019, showing the spatial distribution characteristics of "east heavy and west light" and "south low and north high". iii) Per capita GDP industrial structure, population density, land expansion, and urbanization rate have significant spillover effects on ozone concentration, and the regional spillover effect is greater than the local effect. R&D intensity and education level have a significant negative impact on ozone concentration. iv) There is a decreasing trend in the inhibitory effect of educational attainment and R&D intensity on ozone concentration, and an increasing trend in the promotional effect of population urbanization rate, land expansion, and economic development on ozone concentration. Empirical results suggest a twofold policy meaning: i) to explore the causes behind the distribution of ozone from the new perspective of urbanization, and to further the atmospheric environmental protection system and ii) to eliminate the adverse impacts of ozone pollution on nature and harmonious social development. [ABSTRACT FROM AUTHOR]

Aiming at the problems of high vibration and high noise in gear transmission systems, a model of gear with staggered tooth phase structure(GSTPS) for reducing vibration is proposed. Without changing the overall structure of the gear transmission system, the purpose of reducing mesh stiffness fluctuations is achieved by staggering adjacent gears at a certain angle along the axis, thereby the vibration of the gear transmission system could be reduced. The characterization method of time-varying mesh stiffness of the GSTPS is studied. Then, the impact of different staggered tooth phases(STP) on reducing vibration of the transmission system are researched, and the basis for selecting the optimal STP are obtained. The experimental platform for reducing vibration with STP is established. And some experimental studies were conducted to validate the theoretical model. [ABSTRACT FROM AUTHOR]

The etiopathogenesis of sporadic Parkinson's disease (PD) remains elusive although mitochondrial dysfunction has long been implicated. Recent evidence revealed reduced expression of peroxisome proliferator-activated receptor gamma coactivator-1 α (PGC-1α) and downstream regulated nuclear encoded respiratory complex genes in affected brain tissue from PD patients. We sought to determine whether epigenetic modification of the PGC-1α gene could account for diminished expression. In substantia nigra from PD patients but not control subjects, we show significant promoter-proximal non-canonical cytosine methylation of the PGC-1α gene but not an adjacent gene. As neuroinflammation is a prominent feature of PD and a mediator of epigenetic change, we evaluated whether the pro-inflammatory fatty acid, palmitate, would stimulate PGC-1α promoter methylation in different cell types from the CNS. Indeed, in mouse primary cortical neurons, microglia and astrocytes, palmitate causes PGC-1α gene promoter non-canonical cytosine methylation, reduced expression of the gene and reduced mitochondrial content. Moreover, intracerebroventricular (ICV) injection of palmitate to transgenic human α-synuclein mutant mice resulted in increased PGC-1α promoter methylation, decreased PGC-1α expression and reduced mitochondrial content in substantia nigra. Finally we provide evidence that dysregulation of ER stress and inflammatory signaling is associated with PGC-1α promoter methylation. Together, these data strengthen the connection between saturated fatty acids, neuroflammation, ER stress, epigenetic alteration and bioenergetic compromise in PD.

The etiopathogenesis of sporadic Parkinson's disease (PD) remains elusive although mitochondrial dysfunction has long been implicated. Recent evidence revealed reduced expression of peroxisome proliferator-activated receptor gamma coactivator-1 α (PGC-1α) and downstream regulated nuclear encoded respiratory complex genes in affected brain tissue from PD patients. We sought to determine whether epigenetic modification of the PGC-1α gene could account for diminished expression. In substantia nigra from PD patients but not control subjects, we show significant promoter-proximal non-canonical cytosine methylation of the PGC-1α gene but not an adjacent gene. As neuroinflammation is a prominent feature of PD and a mediator of epigenetic change, we evaluated whether the pro-inflammatory fatty acid, palmitate, would stimulate PGC-1α promoter methylation in different cell types from the CNS. Indeed, in mouse primary cortical neurons, microglia and astrocytes, palmitate causes PGC-1α gene promoter non-canonical cytosine methylation, reduced expression of the gene and reduced mitochondrial content. Moreover, intracerebroventricular (ICV) injection of palmitate to transgenic human α-synuclein mutant mice resulted in increased PGC-1α promoter methylation, decreased PGC-1α expression and reduced mitochondrial content in substantia nigra. Finally we provide evidence that dysregulation of ER stress and inflammatory signaling is associated with PGC-1α promoter methylation. Together, these data strengthen the connection between saturated fatty acids, neuroflammation, ER stress, epigenetic alteration and bioenergetic compromise in PD.

In this study, we sought to improve the efficiency of coal seam gas extraction, master the characteristics of different factors on the liquid carbon dioxide (CO2) phase change blasting cracking radius, and effectively predict the hole spacing. In this study, we used ANSYS/LS-DYNA numerical simulation software to predict the crack radius of liquid CO2 phase change blasting combined with orthogonal design scheme. The results showed that the primary and secondary factors affecting the fracture radius of liquid CO2 phase change blasting were in ground stress, gas pressure, coal firmness coefficient, and gas content. The fracture radius decreased with the increase of in ground stress and decreased with the increase of gas pressure, coal firmness coefficient, and gas content, which was linear. A prediction model for predicting the cracking radius of liquid CO2 phase change blasting based on four groups of different factors was established. Through the double verification of numerical simulation and field industrial test, the cracking radius of liquid CO2 phase change blasting ranged from 2 m to 2.5 m. The maximum error of numerical simulation was 2.8%, and the maximum error of field industrial test was 5.93%. [ABSTRACT FROM AUTHOR]

To study the influence of different factors on the cracking effect of the liquid CO2 phase transition, the mechanics of coal rock crack extension based on liquid CO2 phase change blast loading were studied. Through the application of simulation software to analyze the influence of coal seam physical parameters (in situ stress, gas pressure, modulus of elasticity and strength of coal) and blasting parameters (fracturing pore size and peak pressure of detonation)on the effect of liquid CO2 phase change cracking, the simulation results showed that the cracking effect of liquid CO2 phase change was positively correlated with the changes in gas pressure, elastic modulus, fracture hole diameter and peak vent pressure, negatively correlated with the variation in situ stress and compressive strength, and nearly independent of the tensile strength. In addition, by using Gray correlation analysis to analyze the influence degree of six main factors on the cracking effect, the calculation results showed that the effect of blasting parameters was greater than that of physical parameters. The main controlling factor that affected the blasting effect was the peak pressure of blasting release. By conducting comparative engineering trials with different blasting parameters, the test results showed that the crack effect of the coal seam was positively correlated with the change in fracture hole diameter and peak venting pressure, which was consistent with the results obtained from the simulation. The experimental results and simulation results for the effective radius of coal seam fracturing were basically consistent, with the error between the two types of results falling below 10%. Therefore, the reliability of the blasting numerical model was verified. In summary, the research results provide theoretical guidance for applying and promoting liquid CO2 fracturing technology in coal mines. [ABSTRACT FROM AUTHOR]