Fracture healing is a complex process that involves multiple molecular events, and the regulation mechanism is not fully understood. We acquired miRNA and mRNA transcriptomes of mouse fractures from ...the Gene Expression Omnibus database (GSE76197 and GSE192542) and integrated the miRNAs and genes that were differentially expressed in the control and fracture groups to construct regulatory networks. There were 130 differentially expressed miRNAs and 4,819 differentially expressed genes, including 72 upregulated and 58 downregulated miRNAs, along with 2,855 upregulated and 1964 downregulated genes during early fracture healing. Gene ontology analysis revealed that most of the differentially expressed genes were enriched in the extracellular matrix (ECM) structure and the ECM organization. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment suggested cell cycle, DNA replication, and mismatch repair were involved in the progression of fracture healing. Furthermore, we constructed a molecular network of miRNAs and mRNAs with inverse expression patterns to elucidate the molecular basis of miRNA–mRNA regulation in fractures. The regulatory network highlighted the potential targets, which may help to provide a mechanistic basis for therapies to improve fracture patient outcomes.
Exposure to polycyclic aromatic hydrocarbons (PAHs) from burning “smoky” (bituminous) coal has been implicated as a cause of the high lung cancer incidence in the counties of Xuanwei and Fuyuan, ...China. Little is known about variations in PAH exposure from throughout the region nor how fuel source and stove design affects exposure. Indoor and personal PAH exposure resulting from solid fuel combustion in Xuanwei and Fuyuan was investigated using repeated 24 h particle bound and gas-phase PAH measurements, which were collected from 163 female residents of Xuanwei and Fuyuan. 549 particle bound (283 indoor and 266 personal) and 193 gas phase (all personal) PAH measurements were collected. Mixed effect models indicated that PAH exposure was up to 6 times higher when burning smoky coal than smokeless coal and varied by up to a factor of 3 between different smoky coal geographic sources. PAH measurements from unventilated firepits were up to 5 times that of ventilated stoves. Exposure also varied between different room sizes and season of measurement. These findings indicate that PAH exposure is modulated by a variety of factors, including fuel type, coal source, and stove design. These findings may provide valuable insight into potential causes of lung cancer in the area.
Distal radius fractures (DRFs) have become a public health problem for all countries, bringing a heavier economic burden of disease globally, with China's disease economic burden being even more ...acute due to the trend of an aging population. This study aimed to explore the influencing factors of hospitalization cost of patients with DRFs in traditional Chinese medicine (TCM
) hospitals to provide a scientific basis for controlling hospitalization cost.
With 1306 cases of DRFs patients hospitalized in 15 public TCM
hospitals in two cities of Gansu Province in China from January 2017 to 2022 as the study object, the influencing factors of hospitalization cost were studied in depth gradually through univariate analysis, multiple linear regression, and path model.
Hospitalization cost of patients with DRFs is mainly affected by the length of stay, surgery and operation, hospital levels, payment methods of medical insurance, use of TCM
preparations, complications and comorbidities, and clinical pathways. The length of stay is the most critical factor influencing the hospitalization cost, and the longer the length of stay, the higher the hospitalization cost.
TCM
hospitals should actively take advantage of TCM
diagnostic modalities and therapeutic methods to ensure the efficacy of treatment and effectively reduce the length of stay at the same time, to lower hospitalization cost. It is also necessary to further deepen the reform of the medical insurance payment methods and strengthen the construction of the hierarchical diagnosis and treatment system, to make the patients receive reasonable reimbursement for medical expenses, thus effectively alleviating the economic burden of the disease in the patients with DRFs.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Households in Xuanwei and Fuyuan, China, possess hazardous levels of fine particulate matter with an aerodynamic diameter <2.5 microns (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) from coal ...combustion. Previous studies found that increased exposure to PM2.5 and benzoapyrene (BaP; a PAH) were associated with decreased mitochondrial DNA copy number (mtDNAcn), a marker of oxidative stress. We further evaluated these associations in a cross-sectional study of 148 healthy non-smoking women from Xuanwei and Fuyuan. Personal exposure to PM2.5 and BaP was measured using portable devices. MtDNAcn was measured using qPCR amplification of leukocyte DNA that was collected after air measurements. Linear regression models were used to estimate the associations between personal exposure to PM2.5 and BaP, and mtDNAcn adjusted for age, body mass index (BMI) and fuel type. We found inverse associations between exposure to PM2.5 and BaP, and mtDNAcn. Each incremental log-μg/m3 increase in PM2.5 was associated with a significant decrease in mtDNAcn of -10.3 copies per cell 95% confidence interval (95% CI): -18.6, -2.0; P = 0.02. Additionally, each log-ng/m3 increase in BaP was associated with a significant decrease in mtDNAcn of -5.4 copies per cell (95% CI: -9.9, -0.8, P = 0.02). Age, BMI, fuel type and coal mine type were not significantly associated with mtDNAcn. Exposure to PM2.5 and BaP may alter mitochondrial dynamics in non-smoking Chinese women. MtDNAcn may be a potential mediator of indoor air pollution on chronic disease development.
Silicon carbide (SiC) ceramic is an ideal material for mechanical seal because of its super hardness, high strength, low friction coefficient, good thermal conductivity, and resistance to friction ...and wear. However, due to relatively high resistivity of SiC ceramic, the triboelectric charge caused by rubbing of mechanical seal end-faces could not be released. It is terrible that the accumulation of triboelectric charge could cause electrochemical corrosion, which would accelerate wear. To decrease the resistivity of SiC ceramic is a desire for improving the performance of mechanical seal. In this research, decreasing resistivity of pressureless sintered SiC ceramic was investigated by conductive pathways through semiconductive grains in a body by incorporation of graphene, which has an extremely low resistivity. With the increasing of graphene from 0 to 2 wt.%, the volume resistivity of SiC ceramics sintered with graphene decreased logarithmically from >106 to around 200 Ω·cm, and the bulk density decreased gradually, from 3.132 to 3.039 g/cm3. In order to meet the requirements of mechanical seal, SiC ceramic sintered with 1 wt.% of graphene, for which the volume resistivity is of 397 Ω·cm, the bulk density is of 3.076 g/cm3, and the flexural strength is of 364 MPa, was optimized when all properties were taken into consideration. It is possible to fabricate low-resistivity SiC ceramic as a useful friction pair material for mechanical seal in a special condition, without excessive loss of their excellent mechanical properties by the introduction of partially connected graphene as conductive pathway into semiconducting ceramic.
Lymphoma is a cancer of the lymphoid cells that originated in matured B or T cells. The bioactive natural compounds can efficiently treat this disease with lesser side effects. Thus, in this study, a ...natural stilbene B10 (3-methoxy 5-hydroxy stilbene) isolated from Cajanus cajan (Pigeon Pea) was screened for its anti-proliferative efficacy against 13 cancer cell lines. B10 showed a potential effect on the human lymphoma (Raji) cells. Cytotoxicity analysis of B10 has revealed IC50 concentrations in Raji cells at low doses (18 µM) than other cancer cell lines. The B10 could significantly cause dose and time-dependent inhibition in the proliferation of Raji cells triggering intrinsic apoptosis and S/G1 phase cellular arrest. There was an increased expression of phospho-γ-H2A.X and decreased expression of cyclin D1, causing DNA damage and cell cycle arrest, post- B10 treatments. The mitochondrial membrane potential (MMP) variations observed after B10 treatment led to changes in Bax/Bcl-2 ratio, cytochrome C release, and enhanced expression of cleaved caspase3, 9, PARP-1, and APAF-1. The B10 inhibited the proliferation of Raji cells by significantly downregulating the expression of KRAS, BTK, MDM2, P-JAK2, P-STAT3, PI3K, HDAC1/2, SIRT7, and EP300. The treatment upregulated the tumor suppressor genes PEBP1 and SAP18. Thus, the study could reveal the selective inhibitory effects of B10 on lymphoma, suggesting it as a probable innovative chemotherapeutic agent.
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•B10 induces cytotoxicity in human lymphoma Raji cells causing S/G1 phase arrest.•B10 accelerates DNA damage by activating phospho-γ-H2A.X.•B10 induces tumor suppression by regulating BTK/KRAS/HDAC1/EP300/PEBP1 axis.
Simplification of 3D building models is an important way to improve rendering efficiency. When existing algorithms are directly applied to simplify multi-component models, generally composed of ...independent components with strong topological dependence, each component is simplified independently. The consequent destruction of topological dependence can cause unreasonable separation of components and even result in inconsistent conclusions of spatial analysis among different levels of details (LODs). To solve these problems, a novel simplification method, which considers the topological dependence among components as constraints, is proposed. The vertices of building models are divided into boundary vertices, hole vertices, and other ordinary vertices. For the boundary vertex, the angle between the edge and component (E–C angle), denoting the degree of component separation, is introduced to derive an error metric to limit the collapse of the edge located at adjacent areas of neighboring components. An improvement to the quadratic error metric (QEM) algorithm was developed for the hole vertex to address the unexpected error caused by the QEM’s defect. A series of experiments confirmed that the proposed method could effectively maintain the overall appearance features of building models. Compared with the traditional method, the consistency of visibility analysis among different LODs is much better.
Oxidative stress-mediated ferroptosis and macrophage-related inflammation play an important role in various liver diseases. Here, we explored if and how hepatocyte ferroptosis regulates macrophage ...stimulator of interferon genes (STING) activation in the development of spontaneous liver damage, fibrosis, and tumorigenesis.
We used a transforming growth factor-beta-activated kinase 1 (TAK1) deficiency-induced model of spontaneous liver damage, fibrosis, and tumorigenesis to investigate hepatocyte ferroptosis and its impact on macrophage STING signalling. Primary hepatocytes and macrophages were used for in vitro experiments.
Significant liver injury and increased numbers of intrahepatic M1 macrophages were found in hepatocyte-specific TAK1-deficient (TAK1ΔHEP) mice, peaking at 4 weeks and gradually decreasing at 8 and 12 weeks. Meanwhile, activation of STING signalling was observed in livers from TAK1ΔHEP mice at 4 weeks and had decreased at 8 and 12 weeks. Treatment with a STING inhibitor promoted macrophage M2 polarisation and alleviated liver injury, fibrosis, and tumour burden. TAK1 deficiency exacerbated liver iron metabolism in mice with a high-iron diet. Moreover, consistent with the results from single-cell RNA-Seq dataset, TAK1ΔHEP mice demonstrated an increased oxidative response and hepatocellular ferroptosis, which could be inhibited by reactive oxygen species scavenging. Suppression of ferroptosis by ferrostatin-1 inhibited the activation of macrophage STING signalling, leading to attenuated liver injury and fibrosis and a reduced tumour burden. Mechanistically, increased intrahepatic and serum levels of 8-hydroxydeoxyguanosine were detected in TAK1ΔHEP mice, which was suppressed by ferroptosis inhibition. Treatment with 8-hydroxydeoxyguanosine antibody inhibited macrophage STING activation in TAK1ΔHEP mice.
Hepatocellular ferroptosis-derived oxidative DNA damage promotes macrophage STING activation to facilitate the development of liver injury, fibrosis, and tumorigenesis. Inhibition of macrophage STING may represent a novel therapeutic approach for the prevention of chronic liver disease.
The precise mechanism by which hepatocyte ferroptosis regulates macrophage STING activation in the progression of liver damage, fibrosis, and tumorigenesis remains unclear. Herein, we show that deletion of TAK1 in hepatocytes caused oxidative stress-mediated ferroptosis and macrophage-related inflammation in the development of spontaneous liver injury, fibrosis, and hepatocellular carcinoma.
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•TAK1 deficiency promotes hepatic ferroptosis by inducing oxidative stress and imbalanced iron metabolism.•Oxidative DNA damage from hepatocytes promotes activation of macrophage STING signalling in TAK1-deficient livers.•Targeting macrophage STING signalling or hepatocellular ferroptosis could be beneficial in the treatment of liver injury, fibrosis, and tumours.
Xuanwei and Fuyuan counties in Yunnan Province, China have among the highest lung cancer rates in the country. This has been associated with the domestic combustion of bituminous coal (referred to as ...“smoky” coal). Additionally, significant geographical variation in cancer rates among smoky coal users has been observed, suggesting heterogeneity in fuel source composition and/or combustion characteristics. Research thus far has indicated that smoky coal emits high levels of polycyclic aromatic hydrocarbons (PAHs) and contains high concentrations of fine grained crystalline quartz, however, much of this research is limited in terms of sample size and geographic scope. In order to more fully characterise geochemical and elemental compositions of smoky and smokeless coal use in Xuanwei and Fuyuan, we carried out a large exposure assessment study in households in this region.
Fuel samples representing smoky and “smokeless” (anthracite, the major alternative coal type in the region) coals were collected from 137 homes in Xuanwei and Fuyuan. Rock-Eval, Leco-CS, XRF analysis and electron microscopy were used to establish hydrocarbon content (to represent volatile organic compounds), major and trace element composition and mineral composition respectively. Heterogeneity in coal characteristics between and within coal types was assessed by the Kruskal–Wallis test.
145 coal samples (116 smoky and 29 smokeless coals) were analysed. Statistically significant differences between smoky and smokeless coals with regard to hydrocarbon content, sulfur, trace elements and mineral composition were observed. Of note, smoky coal contained between 5 and 15 times the amount of volatile organic matter and twice the amount of quartz (including respirable quartz) than smokeless coal. Smoky coal generally had lower levels of trace elements (plus aluminium) than smokeless coal. Significant variation was also observed between smoky coal samples from different geographical areas with regard to hydrocarbon content and elemental composition (including aluminium and silicon).
This paper has identified compositional differences between and within smoky and smokeless coals sourced from Xuanwei and Fuyuan counties. A decreased ratio of aluminium to silicon in smoky coal suggests elevated free silica, a finding consistent with observed higher levels of quartz. Elevated volatile organic matter content in smoky coal (when compared to smokeless coal) is consistent with the geochemical expectations for smoky and smokeless coals. These findings also reflect previous observations of elevated volatile compound emissions (notably PAHs) from smoky coal in the area. The observed heterogeneity in coal composition between and within coal types may provide leads to the observed heterogeneity in cancer risk observed in this area.
•Lung cancer in Xuanwei and Fuyuan, China is linked to the use of “smoky” coal.•We investigate the constituents of coal from throughout Xuanwei and Fuyuan.•Smoky coal has high amounts of hydrocarbons and quartz.•Significant geographic variation in smoky coal constituents was observed.
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