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Objective: The excessive proliferation of fibroblast-like synoviocytes (FLSs) is a key inducement for the occurrence and development of rheumatoid arthritis (RA). Hypoxia inducible factor-α (HIF-α) accumulation is involved in the regulation of cell biological functions in the hypoxic microenvironment of synovium. This study aimed to investigate the roles of HIF-α and its level regulator prolyl hydroxylases (PHDs) in FLSs proliferation and to explore the regulatory effect of geniposide (GE). Materials and methods: Adjuvant arthritis rats and RA-FLSs cell line MH7A were taken as the research objects. MH7A cells were incubated in a hypoxic chamber with 2% O2 for hypoxia treatment. CCK-8, FACS, EdU and Western blot assays were performed to evaluate MH7A cells proliferation. Iron assay was conducted to determine intracellular Fe2+ level. Results: MH7A cells proliferation was significantly enhanced under hypoxia, accompanied by an increase of HIF-1α level. Decreased HIF-1α level by PX-478 inhibited MH7A cells proliferation. Furthermore, PHD2 was highly expressed in vivo and in vitro, and played a key role in modulation of HIF-1α protein level, which was confirmed by PHD2 inhibitor IOX4 and proteasome inhibitor MG132. GE treatment alleviated synovial hyperplasia in AA rats and inhibited MH7A cells proliferation with a reduction in HIF-1α level. Fe2+ acts as an enzymatic cofactor to control PHD2 activity. Iron assay showed that GE reversed the decline of Fe2+ level in MH7A cells under hypoxia. Conclusion: GE attenuates abnormal proliferation of RA-FLSs via inhibiting HIF-1α accumulation through enhancement of PHD2 activity. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) has resurged in localized areas in China. Individuals wear masks to prevent the spread of droplets. However, skin barrier damage occurs because of the prolonged use of masks. Objective: To investigate the prevalence and associated risk factors of skin injuries among healthcare workers (HCWs) and the general population during the COVID-19 outbreak. Methods: A multicenter cross-sectional study of skin barrier damage caused by wearing masks was conducted using an online questionnaire between December 10 and December 31, 2020. Data regarding demographics, characteristics of facial skin damage, and information on masks were registered. Multivariate logistic regression was used to analyze factors associated with skin barrier damage, and odds ratios (OR) with 95% confidence intervals (CI) were used to establish correlation strength. Results: A total of 1,538 responses were retrieved from 1,700 questionnaires (response rate, 90.47%), and 1,409 questionnaires were valid (effective response rate, 91.61%). The respondents comprised 567 HCWs (40.24%) and 842 individuals from the general population (59.76%). The prevalence of skin injuries was 46.03% among HCWs and 46.20% among the general population. History of chronic skin disease (OR, 6.01; 95% CI, 4.75–7.75), type of mask used (OR, 2.77; 95% CI, 1.95–3.93), daily wearing time (OR, 1.57; 95% CI, 1.36–1.82), and mask replacement cycle (OR, 0.76; 95% CI, 0.68–0.86) were associated with skin barrier damage. Conclusion: There was a high incidence of skin barrier damage due to prolonged mask use among HCWs and the general population, and treatment and prevention were inadequate. Attention needs to be given to strengthening comprehensive health education and popularization of science. [ABSTRACT FROM AUTHOR]

Objective * To study the structure of the Shelterin quinary complex (Rap1-Poz1-Tpz1-Ccq1-Pot1) in fission yeast Schizosaccharomyces pombe (S. pombe) by negative-staining and electron microscopy. Methods * The Shelterin quinary complex was reconstituted via expression and purification of recombinant proteins in Escherichia coli with histidine-small ubiquitin-related modifier (His-SUMO) and glutathione S-transferase (GST) tags. The target protein complex was isolated via sequential Ni-NTA and glutathione sepharose affinity purification followed by gel filtration chromatography (SuperoseTM6 10/300 GL). The protein samples were stained by 0.75% uranium formate, and then observed by 120 kV transmission electron microscope (TEM) with a magnification of 92 000. The micrographs with good particle dispersity were obtained and the 3D structure of Shelterin complex was reconstructed by single particle image analysis by using EMAN2 and Relion3.0. Finally, UCSF Chimera was used to analyze the reconstruction model of Shelterin complex. Results * The recombinant S. pombe Shelterin quinary complex with high purity, component integrity and good homogeneity was obtained by using a tandem affinity purification scheme with Ni-NTA and GST-based chromatography. Eighty-three micrographs were collected through 120 kV TEM, in which 18 659 particles were picked for 3D model reconstruction. After that, the rough 3D structure of the complex was obtained. Molecular docking of the available crystal structures of Shelterin subcomplex into the reconstructed model revealed that the complex existed in a dimeric form and determined the positioning of each component in the complex. Conclusion * The low-resolution 3D model of S. pombe Shelterin quinary complex (Rap1-Poz1-Tpz1-Ccq1-Pot1) is obtained. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Modern Laboratory Medicine is the property of Journal of Modern Laboratory Medicine Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper elaborates on the production mechanisms of standing waves during high-speed tire rolling and analyzes the relationship between the change of wavelength of sidewall waves and the vehicle velocity, from an oblique wave point of view. A finite element model for a 195/65R15 radial tire is established with the nonlinear analysis software ABAQUS, based on the tire structure and cord parameters. This paper comparatively analyzes the finite element simulation results and experimental results of the tire load-sinkage relation and the load vs inflatable section width relation and finds little difference between the simulation and experimental results. A similar analysis studies the change in the wavelength of sidewall standing waves at different vehicle velocities during high-speed tire rolling. The calculated value by the oblique wave approach, the value by simulation, and the experimental results demonstrate high consistency, concluding that during high-speed tire rolling, the wavelength of sidewall standing waves increases with vehicle velocity. Thus, the accuracy of the finite element model is verified under both static and dynamic conditions. Under a constant tire pressure and load, the impact of velocity change on tire-cord stress during high-speed tire rolling is studied based on the finite element model so as to identity the relation between the cord stress and standing waves. [ABSTRACT FROM AUTHOR]

Context: Development of a reliable and selective anti-inflammatory agent of cyclooxygenase-2 (COX-2), induced or up-regulated by inflammatory/injury stimulus such as IL-1β, TNF-α and LPS in the various types of organs, tissues and cells, with low side effects is a long-standing medicinal chemistry problem with significant social implications. Objective: To target druggable enzymome COX-2 by exploiting NSAIDs and genipin (GEP) in anti-inflammatory infection. Materials and methods: The compound aspirin GEP ester (AGE) was designed by computer-assisted screening, synthesized in the esterification of the acylate derivative and the methylate derivative with Et3N, and evaluated with 20, 40 and 60 mg/kg from days 18 to 24 after immunization in collagen-induced arthritis (CIA) rats by the sequential enzymatic experiments, western-blot analysis and pathological observation methods. Results: AGE exhibited higher binding affinity with COX-1 and displayed the lowest estimated free energy with COX-2 than other ligands built by hanging NSAIDs with GEP, and was characterized by1H NMR,13C NMR and HRMS. AGE was competed against COX-2 with molecule-dependent potencies and selectivity (IC50: 0.36 mM; selectivity index: 275) in the sequential enzymatic experiments and decreased the expression of COX-2 in peripheral blood lymphocytes of CIA rats. AGE (40 and 60 mg/kg) could significantly relieve the secondary hind paw swelling and arthritis index, along with observing AGE attenuated histopathological changes of fibroblast like synovial tissue (FLST) and mesenteric lymph node lymphocytes (MLNL) in CIA rats. Discussion and conclusion: AGE pharmacophore reported herein may be an effective strategy to develop a novel anti-inflammatory agent and potential inhibitor of COX-2. [ABSTRACT FROM AUTHOR]

Copyright of Transactions of the Chinese Society of Agricultural Engineering is the property of Chinese Society of Agricultural Engineering and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The different on-resistance degradations of the p-type lateral extended drain MOS (pLEDMOS) transistor with thick gate oxide for different hot carrier stress conditions have been experimentally investigated for the first time. The difference results from the interface trap generation and the hot electron injection and trapping into the thick gate oxide and field oxide of the pLEDMOS transistor, which has been analyzed in detail using the MEDICI simulator. [ABSTRACT FROM AUTHOR]

Although the efficacy of cancer radiotherapy (RT) can be enhanced by targeted immunotherapy, the immunosuppressive factors induced by radiation on tumor cells remain to be identified. Here, we report that CD47-mediated anti-phagocytosis is concurrently upregulated with HER2 in radioresistant breast cancer (BC) cells and RT-treated mouse syngeneic BC. Co-expression of both receptors is more frequently detected in recurrent BC patients with poor prognosis. CD47 is upregulated preferentially in HER2-expressing cells, and blocking CD47 or HER2 reduces both receptors with diminished clonogenicity and augmented phagocytosis. CRISPR-mediated CD47 and HER2 dual knockouts not only inhibit clonogenicity but also enhance macrophage-mediated attack. Dual antibody of both receptors synergizes with RT in control of syngeneic mouse breast tumor. These results provide the evidence that aggressive behavior of radioresistant BC is caused by CD47-mediated anti-phagocytosis conjugated with HER2-prompted proliferation. Dual blockade of CD47 and HER2 is suggested to eliminate resistant cancer cells in BC radiotherapy. The emergence of tumour adaptive radioresistance can limit the success of radiation therapy and immunotherapy in breast cancer. In this study, the authors demonstrate that CD47 and HER2 are coordinating in tumor response to radiation and that co-blockage of both receptors can eliminate radiorestistant breast cancer cells. [ABSTRACT FROM AUTHOR]