Inhibition of miR-665 alleviates lipopolysaccharide-induced inflammation via up-regulation of SOCS7 in chondrogenic ATDC5 cells

Purpose: To examine the effect and mechanism of action of miR-665 in osteoarthritis.Methods: An in vitro inflammatory injury model of osteoarthritis was established using chondrogenic ATDC5 cells with lipopolysaccharide (LPS) treatment. The expression levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assays (ELISAs) and by quantitative real-time polymerase chain reaction (qRT-PCR). A binding target for miR-665 was predicted using TargetScan and then evaluated using a dual-luciferase reporter assay.Results: Treatment with LPS significantly up-regulated the inflammatory cytokine expressions of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α), in ATDC5 cells (p < 0.01), and the expression of miRNA-665 was significantly increased in LPS-treated ATDC5 cells (p < 0.01).Knockdown of miR-665 down-regulated the expression levels of these inflammatory cytokines. Suppressor of cytokine signaling 7 (SOCS7) was identified as a target of miR-665. Data from qRT-PCR and western-blot analyses indicated that SOCS7 expression was promoted by miR-665  inhibition and inhibited by miR-665 over-expression. LPS treatment significantly decreased the expression of SOCS7 protein in ATDC5 cells (p < 0.01), and over-expression of SOCS7 attenuated the LPS-stimulated inflammatory injury. In addition, over-expression of miR-655 enhanced the inflammatory injury and reversed the protective effect of SOCS7 against LPS-stimulated inflammation.Conclusion: Inhibition of miR-665 alleviated LPS-stimulated inflammatory injury in ATDC5 cells via the up-regulation of SOCS7, suggesting a potential therapeutic target for osteoarthritis. Keywords: MiR-665, Lipopolysaccharide, Inflammation, SOCS7, Chondrogenic, ATDC

Effect of Miao medicine, Jinwujiangu decoction, on IL- 17/IL-23 inflammatory axis of fibroblast-like synoviocytes in rheumatoid arthritis

Purpose: To explore the influence of the Miao medicine, Jinwujiangu decoction, on the interleukin (IL)- 17/IL-23 inflammatory axis of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA).Methods: Synovial tissue samples were randomly divided into a blank control group, high-dose (0.06mg/mL), medium-dose (0.6mg/mL), and low-dose (6.0mg/mL) groups of Jinwujiangu decoction, a leflunomide group, and a tripterygium glycosides group. Proliferation of RA synovial cells was detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Enzyme-linked immunosorbent assay (ELISA) was used to determine the secretion of IL-6, transforming growth factor beta (TGF-β), and IL-17. Real-time polymerase chain reaction was used to evaluate the expression of IL-23R, IL-17R, RAR-related orphan receptor alpha (RORα), RORγt, and signal transducer and activator of transcription (STAT3) mRNA. The protein activities of IL-17R, STAT3 and pSTAT3 were assessed by Western blot assay.Results: Jinwujiangu decoction inhibited the proliferation of RA synovial cells. Treatment with different drug concentrations resulted in downregulation of IL-6, TGF-β, and IL-17 secretion. The expression levels of IL-23R, IL-17R, RORα, RORγt, and STAT3 mRNA in RA-FLS were significantly reduced after intervention with different drugs. Protein expression levels of STAT3, pSTAT3, and IL-17 in the different drug treatment groups were significantly decreased.Conclusion: Jinwujiangu decoction inhibits the secretion of IL-6 and TGF-β in RA-FLS, and intervenes to regulate gene expression of IL-23/IL-17 inflammation axis and suppress immune inflammation. The results of this study provide new evidence for the study of anti-inflammatory mechanism of TCM compound prescription.Keywords: Jinwujiangu decoction, IL-17/IL-23, Fibroblast-like synoviocytes, Rheumatoid arthritis, Ethnomedicin

Complete sequences of KPC-2-encoding plasmid p628-KPC and CTX-M-55-encoding p628-CTXM coexisted in Klebsiella pneumoniae

A carbapenem-resistant Klebsiella pneumoniae strain 628 was isolated from a human case of intracranial infection in a Chinese teaching hospital. Strain 628 produces KPC-2 and CTX-M-55 encoded by two different conjugative plasmids, i.e., the IncFIIK plasmid p628-KPC and the IncI1 plasmid p628-CTXM, respectively. blaKPC-2 is captured by a Tn1721-based unit transposon with a linear structure ΔTn3-ISKpn27-blaKPC-2-ΔISKpn6-ΔTn1721, and this transposon together with a mercury resistance (mer) gene locus constitutes a 34 kb acquired drug-resistance region. blaKPC-2 has two transcription starts (nucleotides G and C located at 39 and 250 bp upstream of its coding region, respectively), which correspond to two promoters, i.e., the intrinsic P1 and the upstream ISKpn27/Tn3-provided P2 with the core -35/-10 elements TAATCC/TTACAT and TTGACA/AATAAT, respectively. blaCTX-M-55 is mobilized in an ISEcp1-blaCTX-M-55-Δorf477 transposition unit and appears to be the sole drug-resistant determinant in p628-CTXM. blaCTX-M-55 possesses a single transcription start (nucleotides G located at 116 bp upstream of its coding region), corresponding to the ISEcp1-provided P1 promoter with the core -35/-10 element TTGAAA/TACAAT. All the above detected promoters display a characteristic of constitutive expression. Coexistence of blaKPC and blaCTX-M in K. pneumoniae has been reported many times, but this is the first report to gain deep insights into genetic platforms, promoters, and expression of the two coexisted bla genes with determination of entire nucleotide sequences of the two corresponding plasmids

An adaptive n-gram transformer for multi-scale scene text recognition

Yan X, Fang Z, Jin Y. An adaptive n-gram transformer for multi-scale scene text recognition. Knowledge-Based Systems. 2023: 110964.While vision transformers have been highly successful in improving the performance in image-based tasks, not much work has been reported on applying transformers to scene text recognition due to the complexities in the visual appearance of multi-scale texts. To fill the gap, this paper proposes an adaptive n-gram transformer for multi-scale scene text recognition (ANT-STR). In ANT-STR, an adaptive n-gram embedding that is able to automatically determine the optimal size of each image patch is designed to fully explore the potential semantic correlations between neighboring visual patches, which is essential for feature extraction from multi-scale scene texts. On top of the adaptive n-gram embedding, a patch-based n-gram attention mechanism is introduced into ANT-STR to further process the feature maps for multi-scale texts. In addition, the loss function is rectified to take into account both multi-scale character-based identification and contextual coherence scoring. Comparative studies are conducted on five widely used benchmark datasets and a new multi-scale scene text dataset collected from tourism scenes in Indonesia. Our experimental results demonstrate that ANT-STR performs considerably better compared to the state-of-the-art, especially in handling complex multi-scale scene texts

Quantifying the Dynamic Sales Impact of Location-Based Mobile Promotion Technologies

Location-based mobile promotion (LMP) is believed to trigger spontaneous and impulsive purchases. This field study quantifies the dynamic impact of LMP, using aggregated daily mobile movie promotions and purchase data from over 3 million real-world users of a large mobile service provider. The developed multivariate time-series models confirm that LMP has a significant contemporaneous impact on movie ticket sales. Bayesian vector autoregressive results also confirm that LMP has significant immediate (next day) and cumulative impacts on sales over the next 9 days. The immediate and cumulative impacts account for 66% of the total effects. These findings suggest that without considering the dynamic effects, practitioners and researchers may substantially under-estimate the value of LMP

Cause marketing effectiveness and the moderating role of price discounts

Can cause marketing (CM) be effective? If so, do price discounts moderate CM effectiveness? Despite the prevalence of linking product sales with donations to charity, field evidence of CM effectiveness is lacking. This is of particular concern for managers who wonder whether the findings of laboratory experiments extend to actual consumer purchases. Using large-scale randomized field experiments with more than 17,000 consumers, this research documents that CM can significantly increase consumer purchases. Notably, the answer to the second question is more complicated. Under the moderating role of price discounts, the impact of CM on sales purchases may follow an inverted U-shaped relationship—that is, strongest when price discounts are moderate rather than deep or absent. Follow-up lab experiments reveal that consumers' warm-glow good feelings from CM represent the underlying process. These findings provide novel insights into the boundary conditions and mechanisms of the sales impact of CM for researchers and managers alike. </jats:p

Mechanical Response of Gasketed Bell-and-Spigot Joint of Concrete Pipeline under Multifield Coupling

Concrete pipe may suffer joint failure under the coupling effect of internal fluid and overlying load, which may lead to pipe leakage. Based on Abaqus and Fluent finite element software, a three-dimensional refined model of drainage pipeline with gasketed bell-and-spigot joints and flow field model inside the pipeline was established. Fully considering the compression of the gasket during pipeline assembly and pipe-soil interaction, the fluid-structure coupling numerical simulation was carried out by using the MpCCI (Mesh-based parallel Code Coupling Interface) platform, and the mechanical response of the concrete pipe joint under the multifield loads coupling effects of burial condition, traffic load, and internal fluid was studied. The accuracy of the coupling model was verified through the full-scale tests that have been carried out. The influences of various factors on the circumferential stress and vertical deformation of the joint were mainly studied. The result reveals that the influence of different working conditions on the circumferential stress of the pipe joint is mainly concentrated on the crown and the invert of the joint, the areas vulnerable to tensile damage. The change of flow field leads to a slight difference in the vertical deformation of the joint, while variation in gasket hardness and cushion compactness has a certain influence on the vertical deformation of the joint. The change of buried depth has a negative correlation to the vertical deformation of the joint, and the change of load position has a significant nonlinear effect. The result provides a theoretical basis for further research on the mechanical mechanism of the pipeline joints during operation